Methods for Production of Aromatic Dicarboxylic Acids and Derivatives Thereof

ABSTRACT

Provided are methods for the production of phthalic acid (PA), isophthalic acid (IP A), terephthalic acid (TP A), and derivatives thereof. The methods are based on the addition of beta propiolactone to furfural or a derivative thereof. Provided are cost effective routes to biobased IP A and derivatives thereof, including terephthalic acid.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/809,612, filed Nov. 10, 2017, which is a national stage ofInternational Application No. PCT/US16/029,020, filed Apr. 22, 2016,which claims the benefit of U.S. Provisional Patent Application No.62/151,589, filed Apr. 23, 2015, and U.S. Provisional Patent App. No.62/187,326, filed Jul. 1, 2015, all of which are incorporated herein byreference in their entireties.

FIELD

The present disclosure relates generally to the production of aromaticdicarboxylic acid compounds and derivatives thereof, and morespecifically to the production of phthalic acid (PA), isophthalic acid(IP A), and terephthalic acid (TP A) and their esters and derivatives.

BACKGROUND

Phthalic acid (PA), Isophthalic acid (IP A), and Terephthalic acid (TPA) and their esters and derivatives are important precursors for thesynthesis of polyesters and other useful materials.

The largest use of IP A and TP A at present is production of highperformance polyamide and polyester polymers. For example, TP A is usedto produce polyethylene terephthalate (PET) which is used extensively inconsumer goods packaging, most prominently in the now ubiquitous clearplastic water bottles. IP A is also used to make polyesters as well ashigh performance polyamides. PA is an important precursor toplasticizers used in a range of polymers. Together PA, IP A, and TP Aare produced on the scale of many millions of tons per year scale byoxidation of xylenes which are obtained from petroleum distillates.

There is strong demand from consumers and consumer goods companies forsustainable alternatives to petroleum-based plastics for packagingapplications. Indeed, Coca Cola® and others have recently introduced PETcontaining biobased monoethylene glycol (MEG). Beverage bottles madefrom this PET are branded as the “Plant Bottle™” and have been wellreceived in the marketplace. Unfortunately, since about 70% of the mass(and 8 out of every 10 carbon atoms) in PET derives from terephthalicand isophthalic acids, replacing petroleum-sourced MEG with biobasedmaterial yields PET that is only about 30% biobased. There is hugeinterest in biobased IP A and TP A to enable fully biobased PETproduction, but to date no economically feasible biobased processesexist.

BRIEF SUMMARY

In one aspect, provided are methods for producing phthalic acid (PA) andisophthalic acid (IP A) and derivatives thereof. In some embodiments,the methods are based on the reaction of beta propiolactone (BPL) withfurfural or a derivative thereof to provide a cyclohexene intermediateas shown in the general scheme below. Furfural derivatives may include,for example, furfural compounds with a protected aldehyde, such as theacetal compounds described herein.

The resulting adducts have all eight carbon atoms connected as neededfor PA and IP A production. Oxidation and dehydration of the adducts(either tandemly or in a series of operations) provides phthalic and/orisophthalic acid (or esters or other derivatives thereof). Sincefurfural is already produced on the scale of millions of tons per yearfrom biobased feedstocks, the methods described herein provide anefficient and practical way to make biobased PA and IP A. Additionally,the methods described herein provide attractive new routes to biobasedTP A.

The renewable content of the diacids produced can be further increasedby utilizing a biobased alpha beta unsaturated carboxylic acid. Forexample, the renewable content of the diacids produced can be furtherincreased by utilizing biobased BPL. BPL can be obtained bycarbonylation of ethylene oxide, which in turn is readily available frombio-sourced ethanol. As such, the present methods provide a practicaland cost-effective route to 100% renewable IP A and TP A.

In another aspect, provided are processes for producing PA and/or IP Abased on the reaction of furfural (or derivatives thereof) with BPL. Incertain embodiments, the methods described herein operate in acontinuous flow format. In certain embodiments, the methods includecontinuously passing a mixture of furfural (or a derivative thereof) andbeta propiolactone through a heated reaction zone, optionally in thepresence of solvent, catalysts, or co-reactants.

In certain embodiments, subsequent oxidation of the addition product offurfural with the BPL is performed in a continuous flow format. Incertain embodiments, two or more reactions selected from the groupconsisting of: dehydration to remove the bridgehead oxygen, dehydrationof the cyclohexene ring to an aryl ring, oxidation of the aldehyde to acarboxylic acid, and esterification or saponification of one or bothcarboxyl groups of the final product occur without isolation ofintermediate products. In certain embodiments, cycloaddition of thefurfural (or a derivative thereof) and BPL occurs in a first fixed bedreactor and the effluent from the reactor is fed to a second reactorwhere the product is heated under dehydrative conditions to effectaromatization of the addition product.

In another aspect, provided are processes for producing PA and/or IP Athat are integrated with an ethylene oxide-based process for BPLproduction. In certain embodiments, the ethylene oxide-based processproduces BPL continuously and a stream from that process is fed to acontinuous reactor where it is contacted with furfural. In certainembodiments, the resulting product is fed to an aromatization reactorwhere it is converted to an aromatic diacid (or mixture of diacids). Incertain embodiments, the process includes a rearrangement reactor forconversion to phthalic acid and/or isophthalic acid to terephthalicacid.

In certain embodiments, provided are integrated processes for theproduction of phthalic and/or isophthalic and/or terephthalic acids fromethylene oxide and furfural, one or both of which may be biobased:

In another aspect, provided are compounds having the formula:

wherein Z is as defined below and described in the classes andsubclasses herein.

In a further aspect, provided are aromatic diacid compositions. Incertain embodiments, provided are isophthalic and/or terephthalic acidcompositions characterized in that they contain or are derived from IP Athat is produced by cycloaddition of an alpha-beta unsaturated acid orester to furfural or a derivative thereof. In certain embodiments, thearomatic diacid compositions are characterized in that five of the eightcarbon atoms in the IP A (and/or TP A) are derived from biobasedfurfural. In certain embodiments, provided aromatic diacid compositionsare characterized in that three of the eight carbon atoms in the IP A(and/or TP A) are derived from a biobased alpha beta unsaturated acid(or a derivative of such a biobased acid). In certain embodiments wherethe alpha beta unsaturated acid is derived from ethylene oxide andcarbon monoxide, one, two or three of the carbon atoms in the alpha betaunsaturated acid may be derived from biobased feedstocks. By extension,aromatic diacid compositions provided herein may contain various degreesof bio content: for example only one biobased carbon atom (e.g. bio COis combined with fossil-based EO to produce acrylic acid which iscombined with non-biobased furfural), two biobased carbon atoms (e.g.biobased ethylene oxide is combined with fossil-based CO to make acrylicacid which is combined with non-biosourced furfural), three biobasedcarbon atoms (e.g., biobased acrylic acid is combined withnon-biosourced furfural), five biobased carbon atoms (bio furfural iscombined with fossil-derived acrylic acid), six biobased carbon atoms(bio furfural is combined with acrylic acid derived from biosourced COand fossil-derived EO), seven biobased carbon atoms (e.g. bio furfuralis combined with acrylic acid derived from biosourced EO andfossil-derived CO), or eight biobased carbon atoms (bio furfural plusbio acrylic acid). This is a unique property of the processes describedherein and enables an IP A (and/or TP A) producer to offer customers arange of price points and bio-content. In a related aspect, provided arePET compositions with varying biocontent derivable by combining the IP Aand/or TP A compositions described with biosourced or fossil-basedmonoethylene glycol (MEG).

In another aspect, provided are processes for producing IP A based onthe cycloaddition of furfural (or derivatives thereof) with acrylic acid(or derivatives thereof). In certain embodiments, the processes operatein a continuous flow format. In certain embodiments, the processincludes continuously passing a mixture of furfural (or a derivativethereof) and an alpha beta unsaturated acid over a bed of solid catalystwhere the catalyst promotes the Diels Alder cycloaddition reaction ofthese two chemicals. In certain embodiments, the oxidation of thecycloaddition product of furfural with the alpha beta unsaturated acidis performed in a continuous flow format. In certain embodiments, two ormore reactions selected from the group consisting of: dehydration toremove the bridgehead oxygen, dehydration of the cyclohexene ring to anaryl ring, oxidation of the aldehyde to a carboxylic acid, andesterification or saponification of one or both carboxyl groups of thefinal product occur without isolation of intermediate products. Incertain embodiments, cycloaddition of the furfural and alpha betaunsaturated acid (or derivative) occurs in a first fixed bed reactor(the Diels Alder reactor) and the effluent from the Diels Alder reactoris fed to a second reactor where the product is heated under oxidativeconditions to effect aromatization of the cycloaddition product.

In another aspect, provided are processes for producing IP A that areintegrated with an ethylene oxide-based process for acrylic acidproduction. In certain embodiments, the ethylene oxide-based processproduces beta propiolactone (BPL) as an intermediate. In certainembodiments, the resulting isophthalic acid is further converted toterephthalic acid. In certain embodiments, the conversion toterephthalic acid is a continuous process fed from the continuousoxidative aromatization reactor.

In certain embodiments, provided are integrated processes for theproduction of isophthalic and/or terephthalic acid from ethylene oxideand furfural, one or both of which may be biobased:

BRIEF DESCRIPTION OF THE FIGURES

The present application can be best understood by reference to thefollowing description taken in conjunction with the accompanyingfigures, in which like parts may be referred to by like numerals.

FIG. 1 depicts an exemplary process to produce compounds of Formulae IVand V from furfural and beta propiolactone.

FIG. 2A depicts exemplary process to produce compounds of Formulae IVand V from furfural and alpha beta unsaturated acids.

FIG. 2B depicts exemplary process to produce compounds of Formula V fromfurfural and alpha beta unsaturated acids.

FIG. 3A depicts an exemplary process to produce compounds of Formulae IIand IIb from furfural and an alcohol.

FIG. 3B depicts an exemplary process to produce4-formyl-7oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid from furfuraland an alcohol.

FIG. 3C depicts an exemplary processes to produce a compound of FormulaI′ from furfural.

FIG. 4A depicts an exemplary process to produce a compound of Formula IVfrom an acetal compound and beta propiolactone.

FIG. 4B depicts an exemplary process to produce a compound of Formula IVfrom an acetal compound and an alpha beta unsaturated acid or ester.

DEFINITIONS

Definitions of specific functional groups and chemical terms aredescribed in more detail below. The chemical elements are identified inaccordance with the Periodic Table of the Elements, CAS version,Handbook of Chemistry and Physics, 75^(th) Ed., inside cover, andspecific functional groups are generally defined as described therein.Additionally, general principles of organic chemistry, as well asspecific functional moieties and reactivity, are described in OrganicChemistry, Thomas Sorrell, University Science Books, Sausalito, 1999;Smith and March March's Advanced Organic Chemistry, 5^(th) Edition, JohnWiley & Sons, Inc., New York, 2001; Larock, Comprehensive OrganicTransformations, VCH Publishers, Inc., New York, 1989; Carruthers, SomeModern Methods of Organic Synthesis, 3^(rd) Edition, CambridgeUniversity Press, Cambridge, 1987.

Certain compounds described herein can comprise one or more asymmetriccenters, and thus can exist in various stereoisomeric forms, e.g.,enantiomers and/or diastereomers. Thus, compounds and compositionsthereof may be in the form of an individual enantiomer, diastereomer orgeometric isomer, or may be in the form of a mixture of stereoisomers.In certain embodiments, the compounds described herein are enantiopurecompounds. In certain other embodiments, mixtures of enantiomers ordiastereomers are provided.

Furthermore, certain compounds as described herein may have one or moredouble bonds that can exist as either a Z or E isomer, unless otherwiseindicated. In some variation, the compounds are individual isomerssubstantially free of other isomers and alternatively, as mixtures ofvarious isomers, e.g., racemic mixtures of enantiomers. In addition tothe above-mentioned compounds per se, provided are compositionscomprising one or more compounds.

As used herein, the term “isomers” includes any and all geometricisomers and stereoisomers. For example, “isomers” include cis- andtrans-isomers, E- and Z-isomers, R- and S-enantiomers, diastereomers,(D)-isomers, (L)-isomers, racemic mixtures thereof, and other mixturesthereof, as falling within the scope of the description herein. Forinstance, a compound may, in some embodiments, be provided substantiallyfree of one or more corresponding stereoisomers, and may also bereferred to as “stereochemically enriched”.

Where a particular enantiomer is preferred, it may, in some embodimentsbe provided substantially free of the opposite enantiomer, and may alsobe referred to as “optically enriched.” “Optically enriched,” as usedherein, means that the compound is made up of a significantly greaterproportion of one enantiomer. In certain embodiments the compound ismade up of at least about 90% by weight of an enantiomer. In someembodiments, the compound is made up of at least about 95%, 97%, 98%,99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer. In someembodiments the enantiomeric excess of provided compounds is at leastabout 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In someembodiments, enantiomers may be isolated from racemic mixtures by anymethod known to those skilled in the art, including chiral high pressureliquid chromatography (HPLC) and the formation and crystallization ofchiral salts or prepared by asymmetric syntheses. See, for example,Jacques, et al., Enantiomers, Racemates and Resolutions (WileyInterscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725(1977); Eliel, E. L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, S. H. Tables of Resolving Agents and OpticalResolutions p. 268 (E. L. Eliel, Ed., Univ. of Notre Dame Press, NotreDame, Ind. 1972).

The terms “halo” and “halogen” as used herein refer to an atom selectedfrom fluorine (fluoro, —F), chlorine (chloro, —Cl), bromine (bromo,—Br), and iodine (iodo, —I).

The term “aliphatic” or “aliphatic group”, as used herein, denotes ahydrocarbon moiety that may be straight-chain (i.e., unbranched),branched, or cyclic (including fused, bridging, and spiro-fusedpolycyclic) and may be completely saturated or may contain one or moreunits of unsaturation, but which is not aromatic. In some variations,the aliphatic group is unbranched or branched. In other variations, thealiphatic group is cyclic. Unless otherwise specified, in somevariations, aliphatic groups contain 1-30 carbon atoms. In certainembodiments, aliphatic groups contain 1-12 carbon atoms. In certainembodiments, aliphatic groups contain 1-8 carbon atoms. In certainembodiments, aliphatic groups contain 1-6 carbon atoms. In someembodiments, aliphatic groups contain 1-5 carbon atoms, in someembodiments, aliphatic groups contain 1-4 carbon atoms, in yet otherembodiments aliphatic groups contain 1-3 carbon atoms, and in yet otherembodiments, aliphatic groups contain 1-2 carbon atoms. Suitablealiphatic groups include, for example, linear or branched, alkyl,alkenyl, and alkynyl groups, and hybrids thereof such as(cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

The term “heteroaliphatic”, as used herein, refers to aliphatic groupswherein one or more carbon atoms are independently replaced by one ormore atoms selected from the group consisting of oxygen, sulfur,nitrogen, phosphorus, or boron. In certain embodiments, one or twocarbon atoms are independently replaced by one or more of oxygen,sulfur, nitrogen, or phosphorus. Heteroaliphatic groups may besubstituted or unsubstituted, branched or unbranched, cyclic or acyclic,and include “heterocycle,” “heterocyclyl,” “heterocycloaliphatic,” or“heterocyclic” groups. In some variations, the heteroaliphatic group isbranched or unbranched. In other variations, the heteroaliphatic groupis cyclic. In yet other variations, the heteroaliphatic group isacyclic.

The term “epoxide”, as used herein, refers to a substituted orunsubstituted oxirane. Substituted oxiranes include, for example,monosubstituted oxiranes, disubstituted oxiranes, trisubstitutedoxiranes, and tetrasubstituted oxiranes. Such epoxides may be furtheroptionally substituted as defined herein. In certain embodiments,epoxides comprise a single oxirane moiety. In certain embodiments,epoxides comprise two or more oxirane moieties.

The term “glycidyl”, as used herein, refers to an oxirane substitutedwith a hydroxyl methyl group or a derivative thereof. The term glycidylas used herein includes moieties having additional substitution on oneor more of the carbon atoms of the oxirane ring or on the methylenegroup of the hydroxymethyl moiety, such substitution may include, forexample, alkyl groups, halogen atoms, and aryl groups. The termsglycidyl ester, glycidyl acrylate, glycidyl ether etc. denotesubstitution at the oxygen atom of the above-mentioned hydroxymethylgroup, i.e. that oxygen atom is bonded to an acyl group, an acrylategroup, or an alkyl group, respectively.

The term “acrylate” or “acrylates”, as used herein, refers to any acylgroup having a vinyl group adjacent to the acyl carbonyl. The termsencompass mono-, di- and tri-substituted vinyl groups. Acrylates mayinclude, for example, acrylate, methacrylate, ethacrylate, cinnamate(3-phenylacrylate), crotonate, tiglate, and senecioate.

The term “polymer”, as used herein, refers to a molecule comprisingmultiple repeating units. In some variations, the polymer is a moleculeof high relative molecular mass, the structure of which comprises themultiple repetition of units derived, actually or conceptually, frommolecules of low relative molecular mass. In certain embodiments, apolymer is comprised of only one monomer species (e.g., polyethyleneoxide). In certain embodiments, the polymer is a copolymer, terpolymer,heteropolymer, block copolymer, or tapered heteropolymer of one or moreepoxides. In one variation, the polymer may be a copolymer, terpolymer,heteropolymer, block copolymer, or tapered heteropolymer of two or moremonomers.

The term “unsaturated”, as used herein, means that a moiety has one ormore double or triple bonds.

The terms “cycloaliphatic”, “carbocycle”, or “carbocyclic”, used aloneor as part of a larger moiety, refer to a saturated or partiallyunsaturated cyclic aliphatic monocyclic, bicyclic, or polycyclic ringsystems, as described herein, having from 3 to 12 members, wherein thealiphatic ring system is optionally substituted as defined above anddescribed herein. Cycloaliphatic groups include, for example,cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl,cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, andcyclooctadienyl. In some embodiments, the cycloalkyl has 3-6 carbons.The terms “cycloaliphatic”, “carbocycle” or “carbocyclic” also includealiphatic rings that are fused to one or more aromatic or nonaromaticrings, such as decahydronaphthyl or tetrahydronaphthyl, where theradical or point of attachment is on the aliphatic ring. In someembodiments, a carbocyclic groups is bicyclic. In some embodiments, acarbocyclic group is tricyclic. In some embodiments, a carbocyclic groupis polycyclic.

The term “alkyl”, as used herein, refers to a saturated hydrocarbonradical. In some variations, the alkyl group is a saturated, straight-or branched-chain hydrocarbon radicals derived from an aliphatic moietycontaining between one and six carbon atoms by removal of a singlehydrogen atom. Unless otherwise specified, in some variations, alkylgroups contain 1-12 carbon atoms. In certain embodiments, alkyl groupscontain 1-8 carbon atoms. In certain embodiments, alkyl groups contain1-6 carbon atoms. In some embodiments, alkyl groups contain 1-5 carbonatoms, in some embodiments, alkyl groups contain 1-4 carbon atoms, inyet other embodiments, alkyl groups contain 1-3 carbon atoms, and in yetother embodiments alkyl groups contain 1-2 carbon atoms. Alkyl radicalsmay include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl,iso-butyl, sec-butyl, sec-pentyl, iso-pentyl, tert-butyl, n-pentyl,neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl,and dodecyl.

The term “alkenyl”, as used herein, denotes a monovalent group having atleast one carbon-carbon double bond. In some variations, the alkenylgroup is a monovalent group derived from a straight- or branched-chainaliphatic moiety having at least one carbon-carbon double bond by theremoval of a single hydrogen atom. Unless otherwise specified, in somevariations, alkenyl groups contain 2-12 carbon atoms. In certainembodiments, alkenyl groups contain 2-8 carbon atoms. In certainembodiments, alkenyl groups contain 2-6 carbon atoms. In someembodiments, alkenyl groups contain 2-5 carbon atoms, in someembodiments, alkenyl groups contain 2-4 carbon atoms, in yet otherembodiments alkenyl groups contain 2-3 carbon atoms, and in yet otherembodiments alkenyl groups contain 2 carbon atoms. Alkenyl groupsinclude, for example, ethenyl, propenyl, butenyl, and1-methyl-2-buten-1-yl.

The term “alkynyl”, as used herein, refers to a monovalent group havingat least one carbon-carbon triple bond. In some variations, the alkynylgroup is a monovalent group derived from a straight- or branched-chainaliphatic moiety having at least one carbon-carbon triple bond by theremoval of a single hydrogen atom. Unless otherwise specified, in somevariations, alkynyl groups contain 2-12 carbon atoms. In certainembodiments, alkynyl groups contain 2-8 carbon atoms. In certainembodiments, alkynyl groups contain 2-6 carbon atoms. In someembodiments, alkynyl groups contain 2-5 carbon atoms, in someembodiments, alkynyl groups contain 2-4 carbon atoms, in yet otherembodiments alkynyl groups contain 2-3 carbon atoms, and in yet otherembodiments alkynyl groups contain 2 carbon atoms. Representativealkynyl groups include, for example, ethynyl, 2-propynyl (propargyl),and 1-propynyl.

The term “carbocycle” and “carbocyclic ring”, as used herein, refer tomonocyclic and polycyclic moieties wherein the rings contain only carbonatoms. Unless otherwise specified, carbocycles may be saturated,partially unsaturated or aromatic, and contain 3 to 20 carbon atoms.Representative carbocyles include, for example, cyclopropane,cyclobutane, cyclopentane, cyclohexane, bicyclo[2,2,1]heptane,norbornene, phenyl, cyclohexene, naphthalene, and spiro[4.5]decane.

The term “aryl”, used alone or as part of a larger moiety as in“aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic andpolycyclic ring systems having a total of five to 20 ring members,wherein at least one ring in the system is aromatic and wherein eachring in the system contains three to twelve ring members. The term“aryl” may be used interchangeably with the term “aryl ring”. In certainembodiments, “aryl” refers to an aromatic ring system which includes,for example, phenyl, naphthyl, and anthracyl, which may bear one or moresubstituents. Also included within the scope of the term “aryl”, as itis used herein, is a group in which an aromatic ring is fused to one ormore additional rings, such as benzofuranyl, indanyl, phthalimidyl,naphthimidyl, phenanthridinyl, and tetrahydronaphthyl.

The terms “heteroaryl” and “heteroar-”, used alone or as part of alarger moiety, e.g., “heteroaralkyl”, or “heteroaralkoxy”, refer togroups having 5 to 14 ring atoms, preferably 5, 6, 9 or 10 ring atoms;having 6, 10, or 14 pi (π) electrons shared in a cyclic array; andhaving, in addition to carbon atoms, from one to five heteroatoms. Theterm “heteroatom” refers to nitrogen, oxygen, or sulfur, and includesany oxidized form of nitrogen or sulfur, and any quaternized form of abasic nitrogen. Heteroaryl groups include, for example, thienyl,furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl,purinyl, naphthyridinyl, benzofuranyl and pteridinyl. The terms“heteroaryl” and “heteroar-”, as used herein, also include groups inwhich a heteroaromatic ring is fused to one or more aryl,cycloaliphatic, or heterocyclyl rings, where the radical or point ofattachment is on the heteroaromatic ring. Examples include indolyl,isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl,benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl,phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl,acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl,tetrahydroquinolinyl, tetrahydroisoquinolinyl, andpyrido[2,3-b]-1,4-oxazin-3(4H)-one. A heteroaryl group may be monocyclicor bicyclic. The term “heteroaryl” may be used interchangeably with theterms “heteroaryl ring”, “heteroaryl group”, or “heteroaromatic”, any ofwhich terms include rings that are optionally substituted. The term“heteroaralkyl” refers to an alkyl group substituted by a heteroaryl,wherein the alkyl and heteroaryl portions independently are optionallysubstituted.

As used herein, the terms “heterocycle”, “heterocyclyl”, “heterocyclicradical”, and “heterocyclic ring” are used interchangeably and may besaturated or partially unsaturated, and have, in addition to carbonatoms, one or more, preferably one to four, heteroatoms, as definedabove. In some variations, the heterocyclic group is a stable 5- to7-membered monocyclic or 7- to 14-membered bicyclic heterocyclic moietythat is either saturated or partially unsaturated, and having, inaddition to carbon atoms, one or more, preferably one to four,heteroatoms, as defined above. When used in reference to a ring atom ofa heterocycle, the term “nitrogen” includes a substituted nitrogen. Asan example, in a saturated or partially unsaturated ring having 0-3heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen maybe N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or ⁺NR(as in N-substituted pyrrolidinyl).

A heterocyclic ring can be attached to its pendant group at anyheteroatom or carbon atom that results in a stable structure and any ofthe ring atoms can be optionally substituted. Examples of such saturatedor partially unsaturated heterocyclic radicals include, for example,tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl,piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl,decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl,diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. Theterms “heterocycle”, “heterocyclyl”, “heterocyclyl ring”, “heterocyclicgroup”, “heterocyclic moiety”, and “heterocyclic radical”, are usedinterchangeably herein, and also include groups in which a heterocyclylring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings,such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, ortetrahydroquinolinyl, where the radical or point of attachment is on theheterocyclyl ring. A heterocyclyl group may be mono- or bicyclic. Theterm “heterocyclylalkyl” refers to an alkyl group substituted by aheterocyclyl, wherein the alkyl and heterocyclyl portions independentlyare optionally substituted.

As used herein, the term “partially unsaturated” refers to a ring moietythat includes at least one double or triple bond. The term “partiallyunsaturated” is intended to encompass rings having multiple sites ofunsaturation, but is not intended to include aryl or heteroarylmoieties, as herein defined.

As described herein, compounds described herein may contain “optionallysubstituted” moieties. In general, the term “substituted”, whetherpreceded by the term “optionally” or not, means that one or morehydrogens of the designated moiety are replaced with a suitablesubstituent. Unless otherwise indicated, an “optionally substituted”group may have a suitable substituent at each substitutable position ofthe group, and when more than one position in any given structure may besubstituted with more than one substituent selected from a specifiedgroup, the substituent may be either the same or different at everyposition. Combinations of substituents envisioned are preferably thosethat result in the formation of stable or chemically feasible compounds.The term “stable”, as used herein, refers to compounds that are notsubstantially altered when subjected to conditions to allow for theirproduction, detection, and, in certain embodiments, their recovery,purification, and use for one or more of the purposes disclosed herein.

In some chemical structures herein, substituents are shown attached to abond which crosses a bond in a ring of the depicted molecule. This meansthat one or more of the substituents may be attached to the ring at anyavailable position (usually in place of a hydrogen atom of the parentstructure). In cases where an atom of a ring so substituted has twosubstitutable positions, two groups may be present on the same ringatom. When more than one substituent is present, each is definedindependently of the others, and each may have a different structure. Incases where the substituent shown crossing a bond of the ring is —R,this has the same meaning as if the ring were said to be “optionallysubstituted” as described in the preceding paragraph.

Suitable monovalent substituents on a substitutable carbon atom of an“optionally substituted” group are independently halogen;—(CH₂)₀₋₄R^(∘); —(CH₂)₀₋₄OR^(∘); —O—(CH₂)₀₋₄C(O)OR; —(CH₂)₀₋₄CH(OR)₂;—(CH₂)₀₋₄SR^(∘); —(CH₂)₀₋₄Ph, which may be substituted with R^(∘);—(CH₂)₀₋₄O(CH₂)₀₋₁Ph which may be substituted with R^(∘); —CH═CHPh,which may be substituted with R^(∘); —NO₂; —CN; —N₃; —(CH₂)₀₋₄N(R^(∘))₂;—(CH₂)₀₋₄N(R^(∘))C(O)R^(∘); —N(R)C(S)R^(∘); —(CH₂)₀₋₄N(R^(∘))C(O)NR^(∘)₂; —N(R^(∘))C(S)NR^(∘) ₂; —(CH₂)₀₋₄N(R^(∘))C(O)OR^(∘);—N(R^(∘))N(R^(∘))C(O)R^(∘); —N(R^(∘))N(R^(∘))C(O)NR^(∘) ₂;—N(R^(∘))N(R^(∘))C(O)OR^(∘); —(CH₂)₀₋₄C(O)R^(∘); —C(S)R^(∘);—(CH₂)₀₋₄C(O)OR^(∘); —(CH₂)₀₋₄C(O)N(R^(∘))₂; —(CH₂)₀₋₄C(O)SR^(∘);—(CH₂)₀₋₄C(O)OSiR^(∘); —(CH₂)₀₋₄C(O)R^(∘); —OC(O)(CH₂)₀₋₄SR—,SC(S)SR^(∘); —(CH₂)₀₋₄SC(O)R; —(CH₂)₀₋₄C(O)NR₂; —C(S)NR^(∘) ₂; —C(S)SRO;—SC(S)SR^(∘), —(CH₂)₀₋₄OC(O)NR^(∘) ₂; —C(O)N(OR^(∘))R^(∘);—C(O)C(O)R^(∘); —C(O)CH₂C(O)R^(∘); —C(NOR^(∘))R^(∘); —(CH₂)₀₋₄SSR^(∘);—(CH₂)₀₋₄S(O)₂R^(∘); —(CH₂)₀₋₄S(O)₂OR^(∘); —(CH₂)₀₋₄OS(O)₂R^(∘);—S(O)₂NR^(∘) ₂; —(CH₂)₄S(O)R^(∘); —N(R^(∘))S(O)₂NR^(∘) ₂;—N(R)S(O)R^(∘); —N(OR^(∘))R; —C(NH)NR^(∘) ₂; —P(O)₂R; —P(O)R^(∘) ₂;—OP(O)R^(∘) ₂; —OP(O)(OR^(∘))₂; SiR^(∘) ₃; —(C₁₋₄ straight or branchedalkylene)O—N(R^(∘))₂; or —(C₁₋₄ straight or branchedalkylene)C(O)O—N(R^(∘))₂, wherein each R^(∘) may be substituted asdefined below and is independently hydrogen, C₁₋₈ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur, or, notwithstanding the definition above, twoindependent occurrences of R^(∘), taken together with their interveningatom(s), form a 3-12-membered saturated, partially unsaturated, or arylmono- or polycyclic ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur, which may be substituted as definedbelow.

Suitable monovalent substituents on R^(∘) (or the ring formed by takingtwo independent occurrences of R^(∘) together with their interveningatoms), are independently halogen, —(CH₂)₀₋₂R^(•), -(haloR^(•)),—(CH₂)₀₋₂OH, —(CH₂)₀₋₂OR^(•), —(CH₂)₀₋₂CH(OR^(•))₂; —O(haloR^(•)), —CN,—N₃, —(CH₂)₀₋₂C(O)R^(•), —(CH₂)₀₋₂C(O)OH, —(CH₂)₀₋₂C(O)OR^(•),—(CH₂)₀₋₄C(O)N(R^(∘))₂; —(CH₂)₀₋₂SR^(•), —(CH₂)₀₋₂SH, —(CH₂)₀₋₂NH₂,—(CH₂)₀₋₂NH₂, —(CH₂)₀₋₂ NHR^(•), —(CH₂)₀₋₂NR^(•) ₂, —NO₂, —SiR^(•) ₃,—OSiR^(•) ₃, —C(O)SR^(•), —(C₁₋₄ straight or branchedalkylene)C(O)OR^(•), or —SSR^(•) wherein each R^(•) is unsubstituted orwhere preceded by “halo” is substituted only with one or more halogens,and is independently selected from C₁₋₄ aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph,or a 5-6-membered saturated, partially unsaturated, or aryl ring having0-4 heteroatoms independently selected from nitrogen, oxygen, andsulfur. Suitable divalent substituents on a saturated carbon atom ofR^(∘) include ═O and ═S.

Suitable divalent substituents on a saturated carbon atom of an“optionally substituted” group include the following: ═O, ═S, ═NNR*₂,═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)₂R, ═NR*, ═NOR*, —O(C(R*₂))₂₋₃O—, or—S(C(R*₂))₂₋₃S—, wherein each independent occurrence of R* is selectedfrom hydrogen, C₁₋₆ aliphatic which may be substituted as defined below,or an unsubstituted 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur. Suitable divalent substituents that are bound tovicinal substitutable carbons of an “optionally substituted” groupinclude: —O(CR*₂)₂₋₃O—, wherein each independent occurrence of R* isselected from hydrogen, C₁₋₆ aliphatic which may be substituted asdefined below, or an unsubstituted 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur.

Suitable substituents on the aliphatic group of R* include halogen,—R^(•), -(haloR^(•)), —OH, —OR^(•), —O(haloR^(•)), —CN, —C(O)OH,—C(O)OR^(•), —NH₂, —NHR^(•), —NR^(•) ₂, or —NO₂, wherein each R^(•) isunsubstituted or where preceded by “halo” is substituted only with oneor more halogens, and is independently C₁₋₄ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur.

Suitable substituents on a substitutable nitrogen of an “optionallysubstituted” group include —R^(†), —NR^(†) ₂, —C(O)R^(†), —C(O)OR^(†),—C(O)C(O)R^(†), —C(O)CH₂C(O)R^(†), —S(O)₂R^(†), —S(O)₂NR^(†) ₂,—C(S)NR^(†) ₂, —C(NH)NR^(†) ₂, or —N(R^(†))S(O)₂R^(†); wherein eachR^(†) is independently hydrogen, C₁₋₆ aliphatic which may be substitutedas defined below, unsubstituted —OPh, or an unsubstituted 5-6-memberedsaturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, or,notwithstanding the definition above, two independent occurrences ofR^(†), taken together with their intervening atom(s) form anunsubstituted 3-12-membered saturated, partially unsaturated, or arylmono- or bicyclic ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur.

Suitable substituents on the aliphatic group of R^(†) are independentlyhalogen, —R^(•), -(haloR^(•)), —OH, —OR^(•), —O(haloR^(•)), —CN,—C(O)OH, —C(O)OR^(•), —NH₂, —NHR^(•), —NR^(•) ₂, or —NO₂, wherein eachR^(•) is unsubstituted or where preceded by “halo” is substituted onlywith one or more halogens, and is independently C₁₋₄ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur.

As used herein, the term “catalyst” refers to a substance the presenceof which increases the rate of a chemical reaction, while not beingconsumed or undergoing a permanent chemical change itself.

As used herein, the term “about” preceding one or more numerical valuesmeans the numerical value ±5%. It should be understood that reference to“about” a value or parameter herein includes (and describes) embodimentsthat are directed to that value or parameter per se. For example,description referring to “about x” includes description of “x” per se.

DETAILED DESCRIPTION Compositions of Matter

In some aspects, provided are compositions comprising compounds ofFormula I:

wherein R^(Y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; an oxygenprotecting group; and a nitrogen protecting group.

In certain embodiments, provided are substantially pure compounds ofFormula I. In certain embodiments, provided are reaction mixtures orprocess streams comprising compounds of Formula I.

In certain embodiments, provided are compositions comprising thecompound of Formula I, wherein R^(Y) is —H. In certain embodiments,provided are compositions comprising a compound of Formula I, whereinR^(Y) is C₁₋₂₀ aliphatic, or where R^(Y) is C₁₋₁₂ aliphatic, or whereR^(Y) is C₁₋₈ aliphatic, or where R^(Y) is C₁₋₆ aliphatic, or whereR^(Y) is C₁₋₄ aliphatic. In certain embodiments, provided arecompositions comprising the compound of Formula I, wherein R^(Y) isselected from the group consisting of methyl, ethyl, propyl, n-butyl,and 2-ethylhexyl.

In certain embodiments, provided is a compound selected from the groupconsisting of:

In certain aspects, provided are compositions comprising compounds ofFormula I′:

wherein Z is selected from the group consisting of —OR^(Y), —Cl, —Br,—NR^(y) ₂, and —SR^(y), wherein each R^(y) is independently hydrogen, oran optionally substituted group selected the group consisting of: acyl;arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀heteroaliphatic having 1-4 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; 5- to I 0-memberedheteroaryl having 1-4 heteroatoms independently selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; an oxygen protectinggroup; and a nitrogen protecting group; or wherein two R^(y) on anitrogen atom may be taken with the nitrogen atom to form an optionallysubstituted 4- to 7-membered heterocyclic ring having 0-2 additionalheteroatoms independently selected from the group consisting ofnitrogen, oxygen, and sulfur.

In certain embodiments, provided are substantially pure compounds ofFormula I′. In certain embodiments, provided are reaction mixtures orprocess streams comprising compounds of Formula I′.

In some variations, Z is —OR^(y). In one variation, R^(y) is —H, and Zis —OH. Thus, in certain embodiments, provided are compositionscomprising the compound of Formula I′, wherein Z is —OH. In certainembodiments, provided are compositions comprising a compound of FormulaI′, wherein Z is —OR^(y) and R^(y) is C₁₋₂₀ aliphatic, or where R^(y) isC₁₋₁₂ aliphatic, or where R^(y) is C₁₋₈ aliphatic, or where R^(y) isC₁₋₆ aliphatic, or where R^(y) is C₁₋₄ aliphatic. In certainembodiments, provided are compositions comprising the compound ofFormula I′, wherein Z is —OR^(y) and R^(y) is selected from the groupconsisting of methyl, ethyl, propyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, provided is a compound selected from the groupconsisting of:

In some variations, Z is —NR^(y)2. In one variation, the two R^(y) maybe taken with the nitrogen atom to which they are attached to form anoptionally substituted 4- to 7-membered heterocyclic ring having 0-2additional heteroatoms independently selected from the group consistingof nitrogen, oxygen, and sulfur.

In other variations, Z is —SR^(y).

In certain embodiments, provided are compositions comprising compoundsof Formula II:

wherein R^(Y) is as defined above and in the classes and subclassesherein, and R^(k) is, independently at each occurrence, selected fromthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; an oxygenprotecting group; and a nitrogen protecting group; where two R^(k) maybe taken with intervening atoms to form an optionally substituted 4- to7-membered heterocyclic ring having 0-2 additional heteroatomsindependently selected from the group consisting of nitrogen, oxygen,and sulfur.

In certain embodiments, provided are substantially pure compounds ofFormula II. In certain embodiments, provided are reaction mixtures orprocess streams comprising compounds of Formula H.

In certain embodiments, provided is a composition comprising compoundsof Formula II, wherein R^(y) is —H. In certain embodiments, provided arecompositions comprising a compound of Formula II, wherein R^(y) is C₁₋₂₀aliphatic, or where R^(y) is C₁₋₁₂ aliphatic, or where R^(y) is C₁₋₈aliphatic, or where R^(y) is C₁₋₆ aliphatic, or where R^(y) is C₁₋₄aliphatic. In certain embodiments, provided are compositions comprisingthe compound of Formula II, wherein R^(Y) is selected from the groupconsisting of methyl, ethyl, propyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, provided are compositions comprising one or morecompounds selected from the group consisting of:

where R^(y) is as defined above and in the classes and subclassesherein.

In certain embodiments, for compounds of Formula II, each R^(k) is thesame as R^(y). In certain embodiments, provided is a compound selectedfrom the group consisting of:

In some variations, provided are compositions comprising compounds ofFormula II′:

wherein each of R^(k) and Z is as defined above and in the classes andsubclasses herein.

In certain embodiments, provided are substantially pure compounds ofFormula II′. In certain embodiments, provided are reaction mixtures orprocess streams comprising compounds of Formula II′.

In certain embodiments, the invention encompasses a compound selectedfrom the group consisting of:

wherein Z is as defined above and in the classes and subclasses herein.

In certain embodiments, provided is a composition comprising compoundsof Formula II′, wherein Z is —OR^(y). In certain embodiments, providedis a composition comprising compounds of Formula II′, wherein Z is —OH.In certain embodiments, provided compositions comprising a compound ofFormula II′, wherein Z is —OR^(y) and R^(y) is C₁₋₂₀ aliphatic, or whereR^(y) is C₁₋₁₂ aliphatic, or where R^(y) is C₁₋₅ aliphatic, or whereR^(y) is C₁₋₆ aliphatic, or where R^(y) is C₁₋₄ aliphatic. In certainembodiments, provided are compositions comprising the compound ofFormula II′, wherein Z is —OR^(y) and R^(y) is selected from the groupconsisting of methyl, ethyl, propyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, for compounds of Formula II′, Z is —OR^(y) andeach of R^(k) is the same as R^(y). In certain embodiments, theinvention encompasses a compound selected from a group consisting of:

In certain embodiments, provided are mixtures comprising compounds ofFormula II and compounds of Formula IIb:

wherein each of R^(y) and R^(k) is as defined above and in the classesand subclasses herein

In certain embodiments, provided are compositions comprising a mixtureof compounds having the formula:

wherein R^(y) is as defined above and in the classes and subclassesherein.

In certain embodiments, for the mixtures of compounds of Formulae II andIIb, each R^(k) and R^(y) is the same. In certain embodiments, providedare compositions containing mixtures of compounds having the formulae:

In certain embodiments, provided are compositions comprising compoundsof Formula III:

wherein Q is a solid support.

In certain embodiments, Q comprises an inorganic support. In certainembodiments, Q comprises an organic resin. In certain embodiments, thelinkage to the solid support Q comprises an ester bond. In certainembodiments, the linkage to the solid support comprises an amide bond.

In certain embodiments, provided are compositions comprising compoundsof Formula IIIa:

wherein each of Q and R^(k) is as defined above and in the classes andsubclasses herein.

In certain embodiments, provided are compositions comprising compoundsof formula:

wherein Q is as defined above and in the classes and subclasses herein.

In certain embodiments, provided are compositions comprising compoundsof formula:

wherein each of Q and R^(k) is as defined above and in the classes andsubclasses herein.

Methods and Making

In some aspects, provided herein are various methods to produce phthalicacid, isophthalic acid, and terephthalic acid, and esters andderivatives thereof In some embodiments, provided are methods to produceisophthalic acid and terephthalic acid, and esters and derivativesthereof, from (i) furfural and (ii) beta propiolactone or an alpha betaunsaturated acid (or an ester, amide or thioester of such an unsaturatedacid).

For example, with reference to FIG. 1, an exemplary pathway is depictedto produce compounds of Formula IV, which may include isophthalic acid,and compounds of Formula V, which may include terephthalic acid, fromfurfural and beta propiolactone. In some variations, as depicted in FIG.3A, furfural and beta propiolactone may combined to produce acetalcompounds. In certain variations, such acetal compounds may behydrolyzed and oxidized to produce compounds of Formula IV, which mayinclude isophthalic acid. The compounds of Formula IV may be isolated.In other variations, the compounds of Formula IV may rearrange undersuitable conditions to produce compounds of Formula V, which may includeterephthalic acid.

With reference to FIG. 2A, an exemplary pathway is depicted to producecompounds of Formula IV, which may include isophthalic acid, andcompounds of Formula V, which may include terephthalic acid, fromfurfural and an alpha beta unsaturated acid or an ester thereof. In somevariations, as depicted in FIG. 3B, acetal compounds may be producedfrom furfural and the alpha beta unsaturated acid or ester thereof incertain variations, such acetal compounds may be oxidized to producecompounds of Formula IV, which may include isophthalic acid. Thecompounds of Formula IV may be isolated. In other variations, thecompounds of Formula IV may rearrange under suitable conditions toproduce compounds of Formula V, which may include terephthalic acid.

With reference to FIG. 2B, an exemplary pathway is depicted to producephthalic acid or esters thereof, and compounds of Formula V, which mayinclude terephthalic acid, from furfural and an alpha beta unsaturatedacid or an ester thereof. In some variations, as depicted in FIG. 3B,acetal compounds may be produced from furfural and the alpha betaunsaturated acid or ester thereof. In certain variations, such acetalcompounds may be oxidized to produce phthalic acid or esters thereof.The phthalic acid or esters may be isolated. In other variations, thephthalic acid or esters may rearrange under suitable conditions toproduce compounds of Formula V, which may include terephthalic acid.

In other aspects, provided herein are methods to produce acetalcompounds. Such acetal compounds may, in certain variations, be used toproduce phthalic acid, isophthalic acid, and terephthalic acid, andesters and derivatives thereof.

For example, with reference to FIGS. 3A-3C, exemplary pathways aredepicted to produce various acetal compounds from furfural and analcohol of formula R^(k)OH or OH—R^(k)—OH. With reference to FIGS. 3Band 3C, the acetal compounds may undergo hydrolysis to produce compoundsthat may be further oxidized to produce compounds of Formula IV, whichmay include isophthalic acid, and compounds of Formula V, which mayinclude terephthalic acid (as depicted in FIGS. 1 and 2).

With reference again to FIGS. 3A-3C, the acetal compounds from furfuraland an alcohol of formula R^(k)—OH of OH—R^(k)—OH may be used in otherreactions to produce compounds of Formulae IV and V. For example, in onevariation, with reference to FIG. 4A, the acetal compound may becombined with beta propiolactone, and the product may undergodehydration and oxidation to produce compounds of Formula IV. In anothervariation, with reference to FIG. 4B, the acetal compound may becombined with an alpha beta unsaturated acid or ester, and the productmay undergo dehydration and oxidation to produce compounds of FormulaIV. In other variations, the compounds of Formula IV may rearrange undersuitable conditions to produce compounds of Formula V.

The various methods to make compounds of Formula IV and V, along withvarious acetal compounds, are described in further detail below.

The reaction of furfural (or acetals thereof) with BPL, alpha betaunsaturated acids or alpha beta unsaturated acid derivatives (such asesters, amides and thioesters) can, in principal produce tworegioisomeric products wherein either: the aldehyde (or acetal) carbonatom of furfural and the carboxylic carbon atom from the BPL or alphabeta unsaturated acid (or derivative thereof) are situated on adjacentcarbon atoms of the cyclohexene ring of the product, or wherein thecarboxylic carbon atom from the BPL or alpha beta unsaturated acid (orderivative thereof) are situated with unsubstituted ring carbonseparating them (as shown in FIG. 3A). Such isomers may be shownseparately in the methods described below, but it is to be understoodthat mixtures of the two regioisomers may also be formed and that suchisomeric mixtures may be separated to isolate a desired isomer. Suchregioisomeric mixtures may also be carried on as a mixture to one ormore subsequent steps. All such variations are contemplated hereinthough all variations may not be explicitly shown in the schemes anddescriptions that follow.

Methods Based on Addition of BPL to Furfural

In certain aspects provided are methods that utilize BPL and furfural asstarting materials.

In certain aspects, provided are methods of making compounds includingadducts of BPL and furfural, as well as aromatized and oxidized productsof such adducts including aromatic dicarboxylic acids.

In some embodiments, provided are methods of making a compound ofFormula I:

the method comprising reacting furfural with beta propiolactone, andoptionally an alcohol of formula HOR^(y) wherein R^(y) is hydrogen, oran optionally substituted moiety selected the group consisting of acyl;arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀heteroaliphatic having 1-4 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; 5- to 10-memberedheteroaryl having 14 heteroatoms independently selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group.

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of Formula I.

In certain embodiments, provided are methods of making a compound ofFormula I:

the method comprising reacting furfural with beta propiolactone, whereR^(y) is as defined above and in the classes and subclasses herein.

In certain embodiments, the methods include reacting furfural with betapropiolactone in the presence of an alcohol. In certain embodimentswhere the reaction is conducted in the presence of an alcohol, theresulting product is an ester of that alcohol (e.g., the alcohol is theform HO—R^(y) where R^(y) is other than —H).

In certain embodiments, where the method comprises reacting furfural andbeta propiolactone in the presence of an alcohol of formula HOR^(y),R^(y) is C₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₅ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments, R^(y) is selectedfrom the group consisting of methyl, ethyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, the reacting of furfural with the betapropiolactone comprises heating a mixture of the furfural and the betapropiolactone. In certain embodiments, the mixture is heated to atemperature between 50° C. and 300° C. In certain embodiments, themixture is heated to a temperature between 50° C. and 150° C., between100° C. and 200° C., between 120° C. and 180° C. or between 150° C. and220° C. In certain embodiments, heating of the mixture of the furfuraland the beta propiolactone comprises flowing the mixture through aheated plug flow reactor.

In certain embodiments, the reacting of furfural with the betapropiolactone comprises contacting a mixture of the two substances witha catalyst. In certain embodiments, the catalyst is a Diels Aldercatalyst. In certain embodiments, the catalyst is a Lewis acidiccatalyst.

In some embodiments, provided are methods of making a compound ofFormula:

the method comprising reacting furfural with beta propiolactone, andoptionally an alcohol of formula HOR^(y), wherein R^(y) is hydrogen, oran optionally substituted moiety selected the group consisting of acyl;arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀heteroaliphatic having 1-4 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; 5- to 10-memberedheteroaryl having 1-4 heteroatoms independently selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group.

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of Formula:

In certain embodiments, the methods include reacting furfural with betapropiolactone in the presence of an alcohol. In certain embodimentswhere the reaction is conducted in the presence of an alcohol, theresulting product is an ester of that alcohol (e.g. the alcohol is theform HO—R^(y) where R^(y) is other than —H.)

In certain embodiments, where the method comprises reacting furfural andbeta propiolactone in the presence of an alcohol of formula HOR^(y) isC₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments, R^(y) is selectedfrom the group consisting of methyl, ethyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, the reacting of furfural with the betapropiolactone comprises heating a mixture of the furfural and the betapropiolactone. In certain embodiments, the mixture is heated to atemperature between 50° C. and 300° C. In certain embodiments, themixture is heated to a temperature between 50° C. and 150° C., between100° C. and 200° C., between 120° C. and 180° C. or between 150° C. and220° C. In certain embodiments, heating of the mixture of the furfuraland the beta propiolactone comprises flowing the mixture through aheated plug flow reactor.

In certain embodiments, the reacting of furfural with the betapropiolactone comprises contacting a mixture of the two substances witha catalyst. In certain embodiments, the catalyst is a Diels Aldercatalyst. In certain embodiments, the catalyst is a Lewis acidiccatalyst.

Methods Based on Adducts of BPL with Acetals of Furfural

In certain aspects provided are methods that utilize BPL and acetals offurfural as starting materials. In certain aspects, provided are methodsof making compounds including adducts of BPL and furfural acetals, aswell as aromatized and oxidized products of such adducts includingaromatic dicarboxylic acids. In some embodiments, provided are methodsof making compounds of Formula IIb:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with beta propiolactone, and optionally        an alcohol of formula HOR^(Y), to produce the compounds of        Formula Bb,    -   wherein:    -   R^(k) is, independently at each occurrence, selected from the        group consisting of acyl; arylalkyl; 6- to 10-membered aryl;        C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 5- to 10-membered heteroaryl having 1-4        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; an oxygen protecting        group; and a nitrogen protecting group; where two R^(k) may be        taken with intervening atoms to form an optionally substituted        4- to 7-membered heterocyclic ring having 0-2 additional        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur, and    -   R^(y) is hydrogen, or an optionally substituted moiety selected        the group consisting of acyl; arylalkyl; 6- to 10-membered aryl;        C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 5- to 10-membered heteroaryl having 1-4        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; and an oxygen        protecting group.

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of Formula IIIb.

In certain embodiments, where the method comprises reacting the acetaland beta propiolactone in the presence of an alcohol of formula HOR^(y)R^(Y) is C₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments, R^(y) is selectedfrom the group consisting of methyl, ethyl, n-butyl, and 2-ethylhexyl.

In certain embodiments provided are methods of making compounds ofFormula IIb:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with beta propiolactone, wherein each        of R^(k) and R^(y) are as defined above and in the classes and        subclasses herein.

In some embodiments, provided are methods of making compounds of FormulaII:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with beta propiolactone, and optionally        an alcohol of formula HOR^(y), to produce the compounds of        Formula II, wherein:        -   R^(k) is, independently at each occurrence, selected from            the group consisting of acyl; arylalkyl; 6- to 10-membered            aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4            heteroatoms independently selected from the group consisting            of nitrogen, oxygen, and sulfur; 5- to 10-membered            heteroaryl having 1-4 heteroatoms independently selected            from the group consisting of nitrogen, oxygen, and sulfur;            4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; an oxygen protecting group;            and a nitrogen protecting group; where two R^(k) may be            taken with intervening atoms to form an optionally            substituted 4- to 7-membered heterocyclic ring having 0-2            additional heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur, and        -   R^(Y) is hydrogen, or an optionally substituted moiety            selected the group consisting of acyl; arylalkyl; 6- to            10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic            having 1-4 heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur; 5- to            10-membered heteroaryl having 1-4 heteroatoms independently            selected from the group consisting of nitrogen, oxygen, and            sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; and an oxygen protecting            group.

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of Formula H.

In certain embodiments, where the method comprises reacting the acetaland beta propiolactone in the presence of an alcohol of formula HOR^(y)R^(y) is C₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments, R^(y) is selectedfrom the group consisting of methyl, ethyl, n-butyl, and 2-ethylhexyl.

In certain embodiments provided are methods of making compounds ofFormula II:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with beta propiolactone, wherein each        of R^(k) and R^(y) are as defined above and in the classes and        subclasses herein.

In certain embodiments, the forming of the acetal and the contactingwith beta propiolactone are performed concomitantly. In certainembodiments, the method comprises treating furfural and betapropiolactone under dehydrating conditions in the presence of an alcoholof formula R^(k)—OH (or HO—R^(k)—OH).

In certain embodiments, provided are methods for making compounds ofFormulae II and/or IIb, wherein each R^(k) is the same as R^(y). Incertain embodiments, such methods comprise the step of contacting betapropiolactone and furfural under dehydrating conditions in the presenceof an alcohol of formula HOR^(k):

In certain embodiments the method comprises reacting the furfural andbeta propiolactone in the presence of an alcohol of formula HOR^(y),wherein R^(y) is C₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic,or C₁₋₆ aliphatic, or C₁₋₄ aliphatic. In certain embodiments, the methodcomprises reacting the furfural and beta propiolactone in the presenceof an alcohol of formula HOR^(y), wherein R^(y) is selected from thegroup consisting of methyl, ethyl, n-butyl, and 2-ethylhexyl.

In some variations, provided are methods of making compounds of FormulaII:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with beta propiolactone, and optionally        an alcohol of formula HOR^(y), to produce the compounds of        Formula II, wherein:        -   R^(k) is, independently at each occurrence, selected from            the group consisting of acyl; arylalkyl; 6- to 10-membered            aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4            heteroatoms independently selected from the group consisting            of nitrogen, oxygen, and sulfur; 5- to 10-membered            heteroaryl having 1-4 heteroatoms independently selected            from the group consisting of nitrogen, oxygen, and sulfur;            4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; an oxygen protecting group;            and a nitrogen protecting group; where two R^(k) may be            taken with intervening atoms to form an optionally            substituted 4- to 7-membered heterocyclic ring having 0-2            additional heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur, and        -   R^(y) is hydrogen, or an optionally substituted moiety            selected the group consisting of acyl; arylalkyl; 6- to            10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic            having 1-4 heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur; 5- to            10-membered heteroaryl having 1-4 heteroatoms independently            selected from the group consisting of nitrogen, oxygen, and            sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; and an oxygen protecting            group.

In one variation of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(Y) is H with respect to the compound of Formula II.

In some embodiments, provided are methods of making a compound ofFormula IV:

the method comprising contacting furfural with BPL, and oxidizing theresulting product, wherein R^(z) is independently —H, R^(y), optionallysubstituted C₁₋₂₀ aliphatic, or optionally substituted aryl.

In certain embodiments, provided are methods of making a compound ofFormula IV:

the method comprising contacting furfural with BPL and oxidizing anddehydrating the resulting product, where R^(z) is as defined above andin the classes and subclasses herein.

In certain embodiments of the provided methods of making compounds ofFormula IV, R^(z) is —H (e.g. compound of Formula IV is isophthalicacid). Where R^(z) is —H, the hydrogen atom may derive from any protonsource present during the dehydration or oxidation processes. Suchproton sources may include, for example, water, alcohols, organic acids,or mineral acids.

In certain embodiments of the provided methods of making compounds ofFormula IV, R^(z) is optionally substituted C₁₋₂₀ aliphatic oroptionally substituted aryl. Where R^(z) is alkyl or aryl it may derivefrom an aliphatic or aromatic alcohol present in the dehydration oroxidation steps.

In some embodiments, provided are methods of making a compound ofFormula IV:

wherein R^(z) is, independently at each occurrence, —H, R^(Y),optionally substituted C₁₋₂₀ aliphatic, or optionally substituted aryl,the method comprising contacting a compound of formula:

-   -   wherein R^(k) is, independently at each occurrence, selected        from the group consisting of acyl; arylalkyl; 6- to 10-membered        aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 5- to 10-membered heteroaryl        having 1-4 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; 4- to 7-membered        heterocyclic having 1-2 heteroatoms independently selected from        the group consisting of nitrogen, oxygen, and sulfur; an oxygen        protecting group; and a nitrogen protecting group; where two        R^(k) may be taken with intervening atoms to form an optionally        substituted 4- to 7-membered heterocyclic ring having 0-2        additional heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur, with BPL, and        dehydrating and oxidizing the resulting product to produce the        compound of Formula IV.

In certain embodiments, provided are methods of making a compound ofFormula IV:

the method comprising contacting a compound of formula:

with BPL and hydrolyzing, dehydrating and oxidizing the resultingproduct, wherein each of R^(k) and R^(z) is as defined above and in theclasses and subclasses herein.

In certain embodiments of the above methods of making compounds ofFormula IV, R^(z) is —H (e.g. compound IV is isophthalic acid). WhereR^(z) is —H, the hydrogen atom may derive from any proton source presentduring the dehydration or oxidation processes. Such proton sources mayinclude for example, water, alcohols, organic acids, or mineral acids.

In certain embodiments of methods of making compounds of Formula IV,R^(z) is optionally substituted C₁₋₂₀ aliphatic or optionallysubstituted aryl. Where R is alkyl or aryl it may derive from analiphatic or aromatic alcohol present in the dehydration or oxidationsteps.

Methods Based on Diels Alder Adducts of Furfural and Furfural Acetals

In another aspect, provided are methods of making compounds includingDiels Alder adducts, aromatized analogs thereof, and aromaticdicarboxylic acids.

In certain aspects the provided methods utilize alpha beta unsaturatedacids (or their esters, amides or thioesters) and furfural as startingmaterials to make aromatic diacids (or intermediates suitable for makingsuch diacids). In certain aspects, provided are methods of makingcompounds including adducts of acrylic acid or its esters and furfural,as well as aromatized and oxidized products of such adducts includingaromatic dicarboxylic acids.

In certain embodiments, provided methods conform to the followingscheme:

wherein Z is selected from the group consisting of —OR^(Y), —Cl, —Br,—NR^(y) ₂, and —SR^(y), wherein each R^(y) is independently hydrogen, oran optionally substituted group selected the group consisting of: acyl;arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀heteroaliphatic having 1-4 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; 5- to 10-memberedheteroaryl having 1-4 heteroatoms independently selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms independently selected from thegroup consisting of nitrogen, oxygen, and sulfur; an oxygen protectinggroup; and a nitrogen protecting group; or wherein two R^(y) on anitrogen atom may be taken with the nitrogen atom to form an optionallysubstituted 4- to 7-membered heterocyclic ring having 0-2 additionalheteroatoms independently selected from the group consisting ofnitrogen, oxygen, and sulfur.

In certain embodiments, Z is OR^(y) and provided are methods depicted inthe following scheme:

wherein R^(y) is as defined above and in the classes and subclassesherein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising reacting furfural with an alpha beta unsaturatedacid or ester, wherein R^(y) is as defined above and in the classes andsubclasses herein.

In certain variations, provided are methods of making a compound offormula:

the method comprising reacting furfural with an alpha beta unsaturatedacid, wherein R^(y) is as defined above and in the classes andsubclasses herein.

In certain embodiments, the methods include reacting furfural with analpha beta unsaturated acid or ester having the formula:

where R^(y) is as defined above and in the classes and subclassesherein.

In certain variations, the methods include reacting furfural with analpha beta unsaturated acid having the formula:

where R^(y) is as defined above and in the classes an su classes herein.

In certain embodiments, R^(y) is —H. In certain embodiments, R^(y) isC₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments R^(y) is selectedfrom the group consisting of: methyl, ethyl, n-butyl, and 2ethylhexyl.

In certain embodiments, provided methods utilize a solid-supported alphabeta unsaturated acid. In certain embodiments, provided are methods ofmaking a compound of Formula III:

the method comprising reacting furfural with an alpha beta unsaturatedacid having the formula:

wherein Q is a solid support.

In certain embodiments, Q comprises an inorganic support. In certainembodiments, Q comprises an organic resin. In certain embodiments, thelinkage to the solid support Q comprises an ester bond. In certainembodiments, the linkage to the solid support comprises an amide bond.

In certain embodiments, provided methods comprise hydrolyzing productsof Formula III to release them from the solid support. In certainembodiments provided methods include contacting the compound of FormulaIII with an alcohol of formula ROR^(y):

wherein each of Q and R^(y) is as defined above and in the classes andsubclasses herein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising treating a compound of formula

with a compound of formula H—OR^(y), where each of Q and R^(y) is asdefined above and in the classes and subclasses herein. In certainembodiments, the reacting of furfural with the alpha beta unsaturatedacid comprises heating a mixture of the furfural and the alpha betaunsaturated acid. In certain embodiments, the mixture is heated to atemperature between 50° C. and 300° C. In certain embodiments, themixture is heated to a temperature between 50° C. and 150° C., between100° C. and 200° C., between 120° C. and 180° C. or between 150° C. and220 OC. In certain embodiments, the heating of the mixture of thefurfural and the alpha beta unsaturated acid comprises flowing themixture through a heated plug flow reactor.

In certain embodiments, the reacting of furfural with the alpha betaunsaturated acid comprises contacting a mixture of the two substanceswith a catalyst. In certain embodiments, the catalyst is a Diels Aldercatalyst. In certain embodiments, the catalyst is a Lewis acidiccatalyst.

In certain aspects the provided methods utilize alpha beta unsaturatedacids (or their esters, amides or thioesters) and acetals of furfural asstarting materials to make aromatic diacids (or intermediates suitablefor making such diacids). In certain aspects, provided are methods ofmaking compounds including adducts of acrylic acid or its esters andfurfural acetals, as well as aromatized and oxidized products of suchadducts including aromatic dicarboxylic acids.

In certain embodiments, provided methods conform to the followingscheme:

wherein each of R^(k) and Z is as defined above and in the classes andsubclasses herein.

In certain embodiments, Z is OR^(y) and provided methods conform to thescheme:

wherein each of R^(k) and R^(y) is as defined above and in the classesand subclasses herein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with an alpha beta unsaturated acid or        ester having formula:

wherein:

-   -   R^(k) is, independently at each occurrence, selected from the        group consisting of acyl; arylalkyl; 6- to 10-membered aryl;        C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 5- to 10-membered heteroaryl having 1-4        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; an oxygen protecting        group; and a nitrogen protecting group; where two R^(k) may be        taken with intervening atoms to form an optionally substituted        4- to 7-membered heterocyclic ring having 0-2 additional        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur, and    -   R^(y) is hydrogen, or an optionally substituted moiety selected        the group consisting of acyl; arylalkyl; 6- to 10-membered aryl;        C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 5- to 10-membered heteroaryl having 1-4        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; and an oxygen        protecting group.

In certain embodiments, R^(y) is —H. In certain embodiments, R^(y) isC₁₋₂₀ aliphatic, or C₁₋₁₂ aliphatic, or C₁₋₈ aliphatic, or C₁₋₆aliphatic, or C₁₋₄ aliphatic. In certain embodiments R^(y) is selectedfrom the group consisting of: methyl, ethyl, n-butyl, and 2ethylhexyl.

In certain embodiments, provided methods utilize a solid-supported alphabeta unsaturated acid to react with a furfural acetal.

In certain embodiments, provided are methods of making a compound ofFormula IIIa:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH (or        HO—R^(k)—OH) under dehydrating conditions to provide an acetal        compound of formula:

and

-   -   b) contacting the acetal with an alpha beta unsaturated acid        having the formula:

where Q is as defined above and in the classes and subclasses herein.

In certain embodiments, provided methods comprise hydrolyzing productsof Formula IIIa to release them from the solid support. In certainembodiments provided methods include contacting the compound of FormulaIIIa with an alcohol of formula HO—R^(y):

wherein each of Q, R^(k) and R^(Y) is as defined above and in theclasses and subclasses herein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising treating a compound of Formula IIIa

with a compound of formula H-QR^(y), wherein each of Q, R^(k) and R^(y)is as defined above and in the classes and subclasses herein.

In certain embodiments, the reacting of the acetal with the alpha betaunsaturated acid or ester comprises heating a mixture of the acetal andthe alpha beta unsaturated acid or ester. In certain embodiments, themixture is heated to a temperature between 50° C. and 300° C. In certainembodiments, the mixture is heated to a temperature between 50° C. and150° C., between 100° C. and 200° C., between 120° C. and 180° C. orbetween 150° C. and 220° C. In certain embodiments, the heating of themixture of the acetal and the alpha beta unsaturated acid or estercomprises flowing the mixture through a heated plug flow reactor.

In certain embodiments, the reacting of acetal with the alpha betaunsaturated acid or ester comprises contacting a mixture of the twosubstances with a catalyst. In certain embodiments, the catalyst is aDiels Alder catalyst. In certain embodiments, the catalyst is a Lewisacidic catalyst.

In some variations, provided are methods of making compounds of FormulaII′:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH under        dehydrating conditions to provide an acetal compound of formula:

and

-   -   b) contacting the acetal with an alpha beta unsaturated acid,        where Z and R^(k) are as defined above and in the classes and        subclasses herein.

In certain embodiments, provided are methods of making compounds ofFormula II′:

the method comprising:

-   -   a) reacting furfural with an alcohol of formula R^(k)—OH under        dehydrating conditions to provide an acetal compound of formula:

and

-   -   b) contacting the acetal with a compound of formula

wherein Z and R^(k) are as defined above and in the classes andsubclasses herein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising treating a compound of formula

with a compound of formula H-QR^(y), where each of Q and R^(y) is asdefined above and in the classes and subclasses herein.

In certain embodiments, provided are methods of making a compound ofFormula I′:

the method comprising hydrolyzing a compound of Formula II′

wherein each of Z and R^(k) are as defined above and in the classes andsubclasses herein.

In certain embodiments, provided are methods of making a compound offormula:

the method comprising hydrolyzing a compound of formula

where each of Q and R^(k) are as defined above and in the classes andsubclasses herein.

The hydrolysis may be performed under any suitable conditions. Forexample, in some variations, the hydrolysis comprises heating the acetalin the presence of water. In certain embodiments, the hydrolysiscomprises contacting the acetal with water in the presence of an acid.In certain embodiments, the hydrolysis comprises contacting the acetalwith water in the presence of a base.

In certain embodiments, provided are methods of making a compound ofFormula IV:

wherein each R^(z) is independently selected from the group consistingof: —H, IV′, optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the method comprising oxidizing a compound of formula:

-   -   wherein R^(y) is hydrogen, or an optionally substituted moiety        selected the group consisting of acyl; arylalkyl; 6- to        10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having        1-4 heteroatoms independently selected from the group consisting        of nitrogen, oxygen, and sulfur; 5- to 10-membered heteroaryl        having 1-4 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; 4- to 7-membered        heterocyclic having 1-2 heteroatoms independently selected from        the group consisting of nitrogen, oxygen, and sulfur; and an        oxygen protecting group.

In certain embodiments, provided are methods of making a compound ofFormula IV:

the method comprising dehydrating and oxidizing a compound of formula:

wherein:

-   -   R^(y) is as defined above and in the classes and subclasses        herein; and each R^(z) is independently selected from the group        consisting of: —H, R^(y), optionally substituted C₁₋₂₀        aliphatic, and optionally substituted aryl.

In certain embodiments, the oxidizing of the compound of formula:

comprises heating the compound in the presence of air. In certainembodiments, the oxidizing step comprises heating the compound in thepresence of air and a solid catalyst. In certain embodiments, theoxidizing step comprises heating the compound in the presence of air andan acidic compound. In certain embodiments, the oxidizing step isperformed under conditions wherein water is continuously removed fromthe reaction mixture.

In certain embodiments, for the compound of formula:

in the methods above, each R^(z) is —H.

In certain embodiments, for the compound of formula:

in the methods above, each R^(z) is —CH₃.

In certain embodiments of the above methods of making compounds ofFormula IV, each R^(z) is —H (e.g. compound of Formula IV is isophthalicacid). Where R^(z) is —H, the hydrogen atom may derive from any protonsource present during the dehydration or oxidation processes. Suchproton sources may include for example, water, alcohols, organic acids,or mineral acids.

In certain embodiments of methods of making compounds of Formula IV,R^(z) is optionally substituted C₁₋₂₀ aliphatic or optionallysubstituted aryl. Where R^(z) is alkyl or aryl it may derive from analiphatic or aromatic alcohol present in the dehydration or oxidationsteps.

In certain embodiments, provided are methods of making a compound ofFormula IV:

wherein each R^(z) is independently selected from the group consistingof: —H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the method comprising contacting furfural with analpha beta unsaturated carboxylic acid, (or an ester, amide or thioesterthereof) and dehydrating and oxidizing the resulting product to producethe compound of Formula IV.

In certain variations, provided are methods of making a compound ofFormula IV:

the method comprising contacting furfural with an alpha beta unsaturatedcarboxylic acid (or a derivative thereof) and oxidizing the resultingproduct, where R^(z) is as defined above and in the classes andsubclasses herein.

In some variations, the alpha beta unsaturated carboxylic acid orderivative thereof is a compound of formula

wherein R^(y) is as defined above and in the classes and subclassesherein

In some variations, the alpha beta unsaturated carboxylic acid isacrylic acid.

In certain embodiments, provided are methods of making a compound ofFormula IV:

wherein each R^(z) is, independently at each occurrence, selected fromthe group consisting of: —H, R^(y), optionally substituted C₁₋₂₀aliphatic, and optionally substituted aryl, the method comprisingcontacting a compound of formula:

wherein each R^(k) is, independently at each occurrence, selected fromthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; an oxygenprotecting group; and a nitrogen protecting group; where two R^(k) maybe taken with intervening atoms to form an optionally substituted 4- to7-membered heterocyclic ring having 0-2 additional heteroatomsindependently selected from the group consisting of nitrogen, oxygen,and sulfur, with an alpha beta unsaturated acid (or an ester, amide, orthioester thereof) and oxidizing the resulting product to produce thecompound of Formula IV.

In certain variations, provided are methods of making a compound ofFormula IV:

the method comprising contacting a compound of formula:

with an alpha beta unsaturated acid (or a derivative thereof) andoxidizing the resulting product, where each of R^(k) and R^(z) is asdefined above and in the classes and subclasses herein.

In some variations, the alpha beta unsaturated carboxylic acid is acompound of formula

wherein R^(y) is as defined above and in the classes and subclassesherein.

In some variations, the alpha beta unsaturated carboxylic acid isacrylic acid.

In certain embodiments of the above methods of making compounds ofFormula IV, R^(z) is —H (e.g. compound of Formula IV is isophthalicacid). Where R^(z) is —H, the hydrogen atom may derive from any protonsource present during the dehydration or oxidation processes. Suchproton sources may include for example, water, alcohols, organic acids,or mineral acids.

In certain embodiments of methods of making compounds of Formula IV,R^(z) is optionally substituted C₁₋₂₀ aliphatic or optionallysubstituted aryl. Where R^(z) is alkyl or aryl it may derive from analiphatic or aromatic alcohol present in the dehydration or oxidationsteps.

Continuous Processes

In another aspect, provided are continuous processes for producingaromatic dicarboxylic acids and precursors thereof.

In some embodiments, provided is a continuous process for the productionof compounds of formula:

the continuous process comprising continuously feeding a reaction zonewith furfural and BPL, and optionally an alcohol of formula HOR^(y),wherein R^(y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group.

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound produced.

In certain embodiments, provided is a continuous process for theproduction of compounds of formula:

the continuous process comprising continuously feeding a reaction zonewith furfural and BPL, where R^(y) is as defined above and in theclasses and subclasses herein.

In certain embodiments, the reaction zone fed with furfural and the BPLis heated. In certain embodiments, the reaction zone is heated to atemperature between 50° C. and 300° C. In certain embodiments, thereaction zone is heated to a temperature between 50° C. and 150° C.,between 100° C. and 200° C., between 120° C. and 180° C., or between150° C. and 220° C.

In certain embodiments, the reaction zone fed with furfural and the BPLcontains a catalyst. In certain embodiments, the reaction zone containsa Lewis acidic catalyst. In certain embodiments, the reaction zonecontains a heterogeneous Lewis acidic catalyst.

In certain embodiments, the process further includes withdrawing aproduct stream containing a compound of formula

from the reaction zone.

In certain embodiments, provided is a continuous process for theproduction of compounds of formula:

the continuous process comprising continuously feeding a reaction zonewith furfural and an alpha beta unsaturated acid or ester, wherein R^(y)is as defined above and in the classes and subclasses herein.

In some variations, the alpha beta unsaturated acid or ester is acompound of formula

wherein R^(y) is as defined above and in the classes and subclassesherein.

In certain embodiments, the reaction zone fed with furfural and thealpha beta unsaturated acid or ester is heated. In certain embodiments,the reaction zone is heated to a temperature between 50° C. and 300° C.In certain embodiments, the reaction zone is heated to a temperaturebetween 50° C. and 150° C., between 100° C. and 200° C., between 120° C.and 180° C., or between 150° C. and 220° C.

In certain embodiments, the reaction zone fed with furfural and thealpha beta unsaturated acid or ester contains a catalyst. In certainembodiments, the reaction zone contains a Lewis acidic catalyst. Incertain embodiments, the reaction zone contains a heterogeneous Lewisacidic catalyst.

In certain embodiments, the process further includes withdrawing aproduct stream containing a Diels Alder adduct of the furfural and analpha beta unsaturated acid or ester from the reaction zone.

In some embodiments, provided is a continuous process for making acompound of Formula IV:

wherein each R^(z) is independently selected from the group consistingof: —H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the process comprising continuously feeding to areaction zone a compound of formula:

wherein R^(y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5 to10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4 to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group, where it is contacted with air, optionally in thepresence of a catalyst to produce the compound of Formula IV.

In certain embodiments, the process includes providing a proton sourcein the reaction zone. In such embodiments, R^(z) in compounds of FormulaIV is —H (e.g. compound of Formula IV is isophthalic acid). Suitableproton sources include water, alcohols, organic acids, and mineralacids.

In certain embodiments, the process includes providing an alcohol ROH inthe reaction zone. Suitable alcohols include aliphatic alcohols (e.g.C₁₋₂₀ alcohols) and aromatic alcohols. When an alcohol is present in thereaction zone, R^(z) in the product may be —H, or R^(z) may be a groupcorresponding to R in the provided alcohol or the product may comprise amixture where R^(z) groups are a mixture of —H and —R.

In certain embodiments, R^(z) in compounds of Formula IV may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present in the reaction zone).

In certain embodiments, provided is a continuous process for making acompound of Formula IV:

the process comprising continuously feeding to a reaction zone acompound of formula:

where it is contacted with air, optionally in the presence of acatalyst.

In certain embodiments, the reaction zone is heated. In certainembodiments, the reaction zone is heated to a temperature between 100°C. and 500° C. In certain embodiments, the reaction zone is heated to atemperature between 100° C. and 200° C., between 120° C. and 180° C.,between 150° C. and 220° C., between 200° C. and 300° C., or between300° C. and 450° C.

In certain embodiments, the reaction zone comprises an acid catalyst. Incertain embodiments, the reaction zone contains sulfuric acid. Incertain embodiments, the reaction zone comprises a heterogeneouscatalyst. In certain embodiments, the reaction zone comprises a solidacid catalyst.

In certain embodiments, the process further includes continuouslywithdrawing a product stream containing isophthalic acid or an esterthereof from the reaction zone. In certain embodiments, the processfurther includes a step of purifying the isophthalic acid (or estersthereof) withdrawn from the reaction zone. In certain embodiments, thepurification includes distillation, crystallization, or a combination ofboth of these.

In some embodiments, provided is a continuous process for making acompound of Formula IV:

wherein R^(z) is independently selected from the group consisting of:—H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the process comprising continuously feeding a firstreaction zone with furfural and BPL, and optionally an alcohol offormula HOR^(y), wherein R^(y) is hydrogen, or an optionally substitutedmoiety selected the group consisting of acyl; arylalkyl; 6- to10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4heteroatoms independently selected from the group consisting ofnitrogen, oxygen, and sulfur; 5- to 10-membered heteroaryl having 1-4heteroatoms independently selected from the group consisting ofnitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic having 1-2heteroatoms independently selected from the group consisting ofnitrogen, oxygen, and sulfur; and an oxygen protecting group, to producea compound of formula:

which is fed to a second reaction zone where it is contacted with air,optionally in the presence of a catalyst to produce the compound ofFormula IV.

In certain embodiments, the process includes providing a proton sourcein the second reaction zone. In such embodiments, R^(z) in compounds ofFormula IV is —H (e.g. compound of Formula IV is isophthalic acid).Suitable proton sources include water, alcohols, organic acids, andmineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe second reaction zone. Suitable alcohols include aliphatic alcohols(e.g. C₁₋₂₀ alcohols) and aromatic alcohols. When an alcohol is presentin the second reaction zone, R^(z) in the product may be —H, or R^(z)may be a group corresponding to R in the provided alcohol or the productmay comprise a mixture where R^(z) groups are a mixture of —H and —R.

In certain embodiments, R^(z) in compounds of Formula IV may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present in the second reaction zone).

In some variations of the foregoing, when the alcohol of formula HOR^(Y)is absent, then R^(y) is H with respect to the compound of formula

In certain embodiments, provided is a continuous process for making acompound of Formula:

the process comprising continuously feeding a first reaction zone withfurfural and BPL, to produce a compound of formula:

which is fed to a second reaction zone where it is contacted with air,optionally in the presence of a catalyst.

In certain embodiments, the first reaction zone is heated. In certainembodiments, the first reaction zone is heated to a temperature between50° C. and 300° C. In certain embodiments, the reaction zone is heatedto a temperature between 50° C. and 150° C., between 100° C. and 200°C., between 120° C. and 180° C., or between 150° C. and 220° C.

In certain embodiments, the first reaction zone contains a catalyst. Incertain embodiments, the first reaction zone contains a Lewis acidiccatalyst. In certain embodiments, the first reaction zone contains aheterogeneous Lewis acidic catalyst.

In certain embodiments, the second reaction zone is heated. In certainembodiments, the second reaction zone is heated to a temperature between100° C. and 500° C. In certain embodiments, the reaction zone is heatedto a temperature between 100° C. and 200° C., between 120° C. and 180°C., between 150° C. and 220° C., between 200° C. and 300° C., or between300° C. and 450° C.

In certain embodiments, the second reaction zone comprises an acidcatalyst. In certain embodiments, the second reaction zone containssulfuric acid. In certain embodiments, the second reaction zonecomprises a heterogeneous catalyst. In certain embodiments, the secondreaction zone comprises a solid acid catalyst.

In certain embodiments, the process further includes continuouslywithdrawing a product stream containing isophthalic acid or an esterthereof from the second reaction zone. In certain embodiments, theprocess further includes purifying the isophthalic acid (or estersthereof) withdrawn from the second reaction zone. In certainembodiments, the purification includes distillation, crystallization, ora combination of both of these.

certain embodiments, provided is a continuous process for making acompound of Formula V:

wherein R^(z) is independently selected from the group consisting of:—H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the process comprising continuously feeding to anoxidizing reaction zone a compound of formula:

wherein it is contacted with air, optionally in the presence of acatalyst to form a compound of Formula IV:

and then, either within the same reaction zone or in a subsequentrearrangement reaction zone, converted to a compound of Formula (V).

In certain embodiments, the process includes providing a proton sourcein the oxidizing reaction zone. In such embodiments, R^(z) in compoundsof Formula V is —H (e.g. compound of Formula V is terephthalic acid).Suitable proton sources include water, alcohols, organic acids, andmineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe oxidizing reaction zone. Suitable alcohols include aliphaticalcohols (e.g. C₁₋₂₀ alcohols) and aromatic alcohols. When an alcohol ispresent in the second reaction zone, R^(z) in the product may be —H, orR^(z) may be a group corresponding to R in the provided alcohol or theproduct may comprise a mixture where R^(z) groups are a mixture of —Hand —R.

In certain embodiments, R^(z) in compounds of V may represent a mixtureincluding groups corresponding to any combination of R^(y) (e.g., fromthe starting material), —H, and R (e.g., from the alcohol ROH if it ispresent in the oxidizing reaction zone).

In certain embodiments, provided is a continuous process for making acompound of Formula V:

the process comprising continuously feeding a first reaction zone withfurfural or a derivative thereof and BPL to provide a product offormula:

which is fed to a second reaction zone where it is contacted with air,optionally in the presence of a catalyst to form a compound of formula;

and then, either within the same reaction zone or in a subsequentrearrangement reaction zone, converted to a compound of Formula V,wherein each of R^(z), and R^(y) are as defined above and in the classesand subclasses herein.

In certain embodiments of this process, the oxidation reaction zone andthe rearrangement reaction zone are contiguous and the process streamflows from a reactor inlet through an oxidation zone and into arearrangement zone. In certain embodiments, there is a temperaturegradient whereby the rearrangement reaction zone is maintained at ahigher temperature than the oxidation reaction zone.

In certain embodiments, the oxidation reaction zone is heated. Incertain embodiments, the oxidation reaction zone is heated to atemperature between 100° C. and 300° C. In certain embodiments, thereaction zone is heated to a temperature between 100° C. and 200° C.,between 120° C. and 180° C., between 150° C. and 220° C., or between200° C. and 250° C.

In certain embodiments, the rearrangement reaction zone is heated. Incertain embodiments, the reaction zone is heated to a temperaturebetween 300° C. and 500° C. In certain embodiments, the reaction zone isheated to a temperature between 300° C. and 400° C., between 350° C. and450° C., between 400° C. and 500° C., between 400° C. and 450° C., orbetween 450° C. and 500° C.

In certain embodiments, the oxidation reaction zone comprises acatalyst. In certain embodiments, the oxidation reaction zone comprisesan acid catalyst. In certain embodiments, the oxidation reaction zonecontains sulfuric acid. In certain embodiments, the oxidation reactionzone comprises a heterogeneous catalyst. In certain embodiments, theoxidation reaction zone comprises a solid acid catalyst.

In certain embodiments, the rearrangement reaction zone comprises acatalyst. In certain embodiments, the rearrangement reaction zonecomprises a transition metal catalyst. In certain embodiments, therearrangement reaction zone contains a cadmium-based catalyst. Incertain embodiments, the rearrangement reaction zone comprises aheterogeneous catalyst. In certain embodiments, the rearrangementreaction zone comprises a heterogeneous transition metal catalyst. Incertain embodiments, the rearrangement reaction zone comprises a solidcadmium-containing catalyst.

In certain embodiments, the process includes providing a proton sourcein the one or more of the oxidation reaction zone and the rearrangementreaction zone. In such embodiments, R^(z) in compounds of Formula V is—H (e.g. compound of Formula V is terephthalic acid). Suitable protonsources include water, alcohols, organic acids, and mineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe one or more of the oxidation reaction zone and the rearrangementreaction zone. Suitable alcohols include aliphatic alcohols (e.g. C₁₋₂₀alcohols) and aromatic alcohols. When an alcohol is present in thesecond reaction zone, R^(z) in the product may be —H, or R^(z) may be agroup corresponding to R in the provided alcohol or the product maycomprise a mixture where R^(z) groups are a mixture of —H and —R.

In certain embodiments, R^(z) in compounds of Formula V may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present one or more reaction zones).

In certain embodiments, the process further includes continuouslywithdrawing a product stream containing terephthalic acid or an esterthereof from the rearrangement reaction zone. In certain embodiments,the process includes withdrawing a product stream containingterephthalic acid or an ester thereof which also contains one or morecoproducts selected from benzene, benzoic acid (or esters thereof),phthalic acid (or esters thereof), and isophthalic acid (or estersthereof). In certain embodiments the process further includes a step ofseparating terephthalic acid (or esters thereof) from one or more ofthese co-products. In certain embodiments the separating processincludes one or more of distillation, and crystallization.

In certain embodiments, provided is a continuous process for theproduction of compounds of Formula IV:

-   -   the continuous process comprising continuously feeding a Diels        Alder reaction zone with furfural and an alpha beta unsaturated        acid or ester, to provide a compound of formula:

andfurther comprising feeding this compound to an oxidation reaction zone,where it is oxidized to a compound of Formula IV, wherein each of R^(z)and R^(y) are as defined above and in the classes and subclasses herein.

In some variations, the alpha beta unsaturated acid or ester is

wherein R^(y) is as defined above and in the classes and subclassesherein.

In certain embodiments, the Diels Alder reaction zone is heated. Incertain embodiments, the Diels Alder reaction zone is heated to atemperature between 50° C. and 300° C. In certain embodiments, the DielsAlder reaction zone is heated to a temperature between 50° C. and 150°C., between 100° C. and 200° C., between 120° C. and 180° C., or between150° C. and 220° C.

In certain embodiments, the Diels Alder reaction zone contains acatalyst. In certain embodiments, the Diels Alder reaction zone containsa Lewis acidic catalyst. In certain embodiments, the reaction zonecontains a heterogeneous Lewis acidic catalyst.

In certain embodiments, the process further includes purifying a productstream obtained from the Diels Alder reaction zone prior to inputting itto the oxidation reaction zone. In certain embodiments, the purifyingstep comprises distilling away unreacted furfural or alpha betaunsaturated acids or esters. In certain embodiments, these materials arereturned to the inlet of the Diels Alder reaction zone for furtherconversion. In certain embodiments, the purifying comprisescrystallizing Diels Alder adducts from the product stream and separatingthe crystalline material from dissolved materials. In certainembodiments, the dissolved fraction is returned to the inlet of theDiels Alder reaction zone.

In some embodiments, provided is a continuous process for the productionof compounds of Formula IV:

the continuous process comprising continuously feeding a first reactionzone with furfural and BPL, and optionally an alcohol of formulaHOR^(y), to provide a compound of formula:

andwherein R^(y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group; and feeding this compound to an oxidation reactionzone, where it is oxidized to a compound of Formula IV.

In certain embodiments, the process includes providing a proton sourcein the oxidizing reaction zone. In such embodiments, R^(z) in compoundsof Formula IV is —H (e.g. compound of Formula IV is isophthalic acid).Suitable proton sources include water, alcohols, organic acids, andmineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe oxidizing reaction zone. Suitable alcohols include aliphaticalcohols (e.g. C₁₋₂₀ alcohols) and aromatic alcohols. When an alcohol ispresent in the second reaction zone, R^(z) in the product may be —H, orR^(z) may be a group corresponding to R in the provided alcohol or theproduct may comprise a mixture where R^(z) groups are a mixture of —Hand —R.

In certain embodiments, R^(z) in compounds of Formula IV may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present in the oxidizing reaction zone).

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of formula

In certain embodiments, provided is a continuous process for theproduction of compounds of formula:

the continuous process comprising continuously feeding a first reactionzone with furfural and BPL, to provide a compound of formula:

andfurther comprising feeding this compound to an oxidation reaction zone,where it is oxidized to a compound of formula

In certain embodiments, the first reaction zone is heated. In certainembodiments, the first reaction zone is heated to a temperature between50° C. and 300° C. In certain embodiments, the first reaction zone isheated to a temperature between 50° C. and 150° C., between 100° C. and200° C., between 120° C. and 180° C., or between 150° C. and 220° C.

In certain embodiments, the first reaction zone contains a catalyst. Incertain embodiments, the first reaction zone contains a Lewis acidiccatalyst. In certain embodiments, the first reaction zone contains aheterogeneous Lewis acidic catalyst.

In certain embodiments, the process further includes purifying a productstream obtained from the first zone prior to inputting it to theoxidation reaction zone. In certain embodiments the purifying stepcomprises distilling away unreacted furfural or alpha beta unsaturatedacids or esters. In certain embodiments, these materials are returned tothe inlet of the first reaction zone for further conversion. In certainembodiments, the step of purifying comprises crystallizing product fromthe product stream and separating the crystalline material fromdissolved materials. In certain embodiments, the dissolved fraction isreturned to the inlet of the first reaction zone.

In certain embodiments, the oxidation reaction zone is heated. Incertain embodiments, the oxidation reaction zone is heated to atemperature between 100° C. and 500° C. In certain embodiments, theoxidation reaction zone is heated to a temperature between 100° C. and200° C., between 120° C. and 180° C., between 150° C. and 220° C.,between 200° C. and 300° C., or between 300° C. and 450° C.

In certain embodiments, the oxidation reaction zone comprises an acidcatalyst. In certain embodiments, the oxidation reaction zone containssulfuric acid. In certain embodiments, the oxidation reaction zonecomprises a heterogeneous catalyst. In certain embodiments, theoxidation reaction zone comprises a solid acid catalyst.

In certain embodiments, the process further includes continuouslywithdrawing a product stream containing isophthalic acid or an esterthereof from the oxidation reaction zone. In certain embodiments, theprocess further includes a step of purifying the isophthalic acid (oresters thereof) withdrawn from the oxidation reaction zone. In certainembodiments, the purification includes distillation, crystallization, ora combination of both of these.

In some embodiments, provided is a continuous process for making acompound of Formula V:

wherein R^(z) is independently selected from the group consisting of:—H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the continuous process comprising continuously feedinga Diels Alder reaction zone with furfural and an alpha beta unsaturatedacid or ester, to provide a compound of formula:

wherein R^(y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group; feeding the compound to an oxidation reaction zonewhere it is contacted with air, optionally in the presence of acatalyst, to form a compound of Formula IV:

andfeeding the compound of Formula IV to a rearrangement reaction zone,where it is converted to a compound of Formula V.

In certain embodiments, the process includes providing a proton sourcein the oxidizing reaction zone. In such embodiments, R^(z) in compoundsof Formula V is —H (e.g. compound of Formula V is terephthalic acid).Suitable proton sources include water, alcohols, organic acids, andmineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe oxidizing reaction zone. Suitable alcohols include aliphaticalcohols (e.g. C₁₋₂₀ alcohols) and aromatic alcohols. When an alcohol ispresent in the second reaction zone, R^(z) in the product may be —H, orR^(z) may be a group corresponding to R in the provided alcohol or theproduct may comprise a mixture where R^(z) groups are a mixture of —Hand —R.

In certain embodiments, R^(z) in compounds of Formula V may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present in the oxidizing reaction zone).

In certain embodiments, provided is a continuous process for making acompound of formula:

the continuous process comprising continuously feeding a Diels Alderreaction zone with furfural and an alpha beta unsaturated acid or ester,to provide a compound of formula:

which is then fed to an oxidation reaction zone where it is contactedwith air, optionally in the presence of a catalyst, to form a compoundof formula:

which is then fed to a rearrangement reaction zone, where it isconverted to a compound of formula:

wherein each of R^(z), and R^(y) are as defined above and in the classesand subclasses herein.

In certain embodiments of the processes described herein, the Die IsAlder reaction zone is heated. In certain embodiments, the Diels Alderreaction zone is heated to a temperature between 50° C. and 300° C. Incertain embodiments, the Diels Alder reaction zone is heated to atemperature between 50° C. and 150° C., between 100° C. and 200° C.,between 120° C. and 180° C., or between 150° C. and 220° C.

In certain embodiments, the Diels Alder reaction zone contains acatalyst. In certain embodiments, the Diels Alder reaction zone containsa Lewis acidic catalyst. In certain embodiments, the reaction zonecontains a heterogeneous Lewis acidic catalyst.

In certain embodiments, the processes described herein further includepurifying a product stream obtained from the Diels Alder reaction zoneprior to inputting it to the oxidation reaction zone. In certainembodiments the purifying step comprises distilling away unreactedfurfural or alpha beta unsaturated acids or esters. In certainembodiments, these materials are returned to the inlet of the DielsAlder reaction zone for further conversion. In certain embodiments, thestep of purifying comprises crystallizing Diels Alder adducts from theproduct stream and separating the crystalline material from dissolvedmaterials. In certain embodiments, the dissolved fraction is returned tothe inlet of the Diels Alder reaction zone.

In some embodiments, provided is a continuous process for making acompound of Formula V:

wherein R^(z) is independently selected from the group consisting of:—H, R^(y), optionally substituted C₁₋₂₀ aliphatic, and optionallysubstituted aryl, the continuous process comprising continuously feedinga first reaction zone with furfural and BPL, and optionally an alcoholof formula HOR^(y), to provide a compound of formula:

andwherein R^(y) is hydrogen, or an optionally substituted moiety selectedthe group consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independentlyselected from the group consisting of nitrogen, oxygen, and sulfur; 5-to 10-membered heteroaryl having 1-4 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur; and an oxygenprotecting group, to provide a compound of formula:

feeding the compound to an oxidizing reaction zone where it is contactedwith air, optionally in the presence of a catalyst, to form a compoundof Formula IV:

which is then fed to a rearrangement reaction zone, where it isconverted to a compound of Formula V.

In certain embodiments, the process includes providing a proton sourcein the one or more of the oxidation reaction zone and the rearrangementreaction zone. In such embodiments, R^(z) in compounds of Formula V is—H (e.g. compound of Formula V is terephthalic acid). Suitable protonsources include water, alcohols, organic acids, and mineral acids.

In certain embodiments, the process includes providing an alcohol ROH inthe one or more of the oxidation reaction zone and the rearrangementreaction zone. Suitable alcohols include aliphatic alcohols (e.g. C₁₋₂₀alcohols) and aromatic alcohols. When an alcohol is present in thesecond reaction zone, R^(z) in the product may be —H, or R^(z) may be agroup corresponding to R in the provided alcohol or the product maycomprise a mixture where R^(z) groups are a mixture of —H and —R.

In certain embodiments, R^(z) in compounds of Formula V may represent amixture including groups corresponding to any combination of R^(y)(e.g., from the starting material), —H, and R (e.g., from the alcoholROH if it is present one or more reaction zones).

In some variations of the foregoing, when the alcohol of formula HOR^(y)is absent, then R^(y) is H with respect to the compound of formula

In certain embodiments, provided is a continuous process for making acompound of formula:

the continuous process comprising continuously feeding a first reactionzone with furfural and BPL, to provide a compound of formula:

which is then fed to an oxidizing reaction zone where it is contactedwith air, optionally in the presence of a catalyst, to form a compoundof formula:

which is then fed to a rearrangement reaction zone, where it isconverted to a compound of formula:

where each of R^(z) and R^(y) are independently as defined above and inthe classes and subclasses herein.

In certain embodiments of the processes described herein, the firstreaction zone is heated. In certain embodiments, the first reaction zoneis heated to a temperature between 50° C. and 300° C. In certainembodiments, the first reaction zone is heated to a temperature between50° C. and 150° C., between 100° C. and 200° C., between 120° C. and180° C., or between 150° C. and 220° C.

In certain embodiments of the processes described herein, the firstreaction zone contains a catalyst. In certain embodiments, the firstreaction zone contains a Lewis acidic catalyst. In certain embodiments,the first reaction zone contains a heterogeneous Lewis acidic catalyst.

In certain embodiments, the processes described herein further includepurifying a product stream obtained from the first reaction zone priorto inputting it to the oxidation reaction zone. In certain embodimentsthe purifying step comprises distilling away unreacted furfural, BPL, oralpha beta unsaturated acids or esters. In certain embodiments, thesematerials are returned to the inlet of the first reaction zone forfurther conversion. In certain embodiments, the step of purifyingcomprises crystallizing products from the product stream and separatingthe crystalline material from dissolved materials. In certainembodiments, the material from the dissolved fraction is returned to theinlet of the first reaction zone.

In certain embodiments of the processes described herein, the oxidationreaction zone is heated. In certain embodiments, the oxidation reactionzone is heated to a temperature between 100° C. and 300° C. In certainembodiments, the reaction zone is heated to a temperature between 100°C. and 200° C., between 120° C. and 180° C., between 150° C. and 220°C., or between 200° C. and 250° C.

In certain embodiments of the processes described herein, the oxidationreaction zone comprises a catalyst. In certain embodiments, theoxidation reaction zone comprises an acid catalyst. In certainembodiments, the oxidation reaction zone contains sulfuric acid. Incertain embodiments, the oxidation reaction zone comprises aheterogeneous catalyst. In certain embodiments, the oxidation reactionzone comprises a solid acid catalyst.

In certain embodiments of the processes described herein, therearrangement reaction zone is heated. In certain embodiments, thereaction zone is heated to a temperature between 300° C. and 500° C. Incertain embodiments, the reaction zone is heated to a temperaturebetween 300° C. and 400° C., between 350° C. and 450° C., between 400°C. and 500° C., between 400° C. and 450° C., or between 450° C. and 500°C.

In certain embodiments, the rearrangement reaction zone comprises acatalyst. In certain embodiments, the rearrangement reaction zonecomprises a transition metal catalyst. In certain embodiments, therearrangement reaction zone contains a cadmium-based catalyst. Incertain embodiments, the rearrangement reaction zone comprises aheterogeneous catalyst. In certain embodiments, the rearrangementreaction zone comprises a heterogeneous transition metal catalyst. Incertain embodiments, the rearrangement reaction zone comprises a solidcadmium-containing catalyst.

In certain embodiments of the processes described herein, the oxidationreaction zone and the rearrangement reaction zone are contiguous and theprocess stream flows from a reactor inlet through an oxidation zone andinto a rearrangement zone. In certain embodiments, there is atemperature gradient whereby the rearrangement reaction zone ismaintained at a higher temperature than the oxidation reaction zone.

In certain embodiments of the processes described herein, the product ofthe oxidation reaction zone is converted to a salt prior to being fed tothe rearrangement reaction zone. In certain embodiments of this process,the product of the oxidation reaction zone is converted to its alkalimetal salt prior to being fed to the rearrangement reaction zone. Incertain embodiments of this process, the product of the oxidationreaction zone is converted to its potassium salt prior to being fed tothe rearrangement reaction zone. In some variations of this process, theproduct of the oxidation reaction zone is converted to its alkali metalsalt prior to being fed to the rearrangement reaction zone. In othervariations of this process, the stream withdrawn from the rearrangementreaction zone is subsequently treated with an acid to convert the alkalimetal salt of the terephthalic acid back to its acid form, or optionallywith inclusion of an appropriate alcohol or similar reagent to aterephthalate ester. In certain embodiments of this process, the streamwithdrawn from the rearrangement reaction zone is subsequently treatedwith an acid to convert the alkali metal salt of the terephthalic acidback to its acid form, or optionally with inclusion of an appropriatealcohol or similar reagent to form a terephthalate ester.

In certain embodiments, the processes described herein further includecontinuously withdrawing a product stream containing terephthalic acidor an ester thereof from the rearrangement reaction zone. In certainembodiments, the process includes withdrawing a product streamcontaining terephthalic acid (or an ester or salt thereof) which alsocontains one or more co-products selected from benzene, benzoic acid (oresters or salts thereof), phthalic acid (or esters thereof), andisophthalic acid (or esters thereof). In certain embodiments, theprocess further includes a step of separating terephthalic acid (oresters thereof) from one or more of these co-products. In certainembodiments, the separating process includes one or more ofdistillation, and crystallization.

Polymer Compositions

In another aspect, provided are biobased monomers and polymercompositions derived therefrom.

In certain embodiments, provided are polymer compositions comprisingisophthalic acid and esters thereof, characterized by their biobasedcarbon content. In certain embodiments, such compositions comprisecompounds having a formula:

and characterized in that carbon atoms I through 5 are derived frombiobased furfural. In certain embodiments of such compositions, R^(z) is—H. In certain embodiments of such compositions, R^(z) is C₁₋₂₀aliphatic. In certain embodiments of such compositions R^(z) is selectedfrom the group consisting of: methyl, ethyl, n-butyl, and 2-ethylhexyl.

In certain embodiments, provided is biobased terephthalic acidcompositions derived by rearrangement of such isophthalic acidcompositions (or esters thereof).

In certain embodiments, such compositions comprise compounds having aformula:

and characterized in that carbon atoms 6 through 8 are derived from abiobased alpha beta unsaturated acid. In certain embodiments of suchcompositions, R^(z) is —H. In certain embodiments of such compositions,R^(z) is C₁₋₂₀ aliphatic. In certain embodiments of such compositions,R^(z) is selected from the group consisting of: methyl, ethyl, n-butyl,and 2ethylhexyl.

In certain embodiments, provided are biobased terephthalic acidcompositions derived by rearrangement of such isophthalic acidcompositions (or esters thereof).

In certain embodiments, provided are isophthalic acid compositionscharacterized in that five carbon atoms are derived from biobasedfurfural and the remaining three carbon atoms are derived from biobasedacrylic acid. In certain embodiments, provided are biobased isophthalateesters derived from such isophthalic acid compositions. In certainembodiments, provided are biobased terephthalic acid compositionsderived by rearrangement of such isophthalic acid compositions (oresters thereof).

In certain embodiments, provided are biobased polymers derived from thebiobased isophthalic acid and terephthalic acid compositions describedabove. In certain embodiments, such polymers comprise polyesters. Incertain embodiments, such polymers comprise polyamides.

In certain embodiments, provided are biobased polyester compositionscomprising the biobased isophthalic acid and/or terephthalic acidcompositions described above. In certain embodiments, such polyestersare the result of condensation of the acids (or esters thereof) withdiols. In certain embodiments, the diol is a C₂₋₂₀ aliphatic diol. Incertain embodiments, the diol is selected from the group consisting of:ethylene glycol, propylene glycol, 1,3-propanediol, 1,4 butanediol, andisosorbide. In certain embodiments, the diol is an aromatic diol. Incertain embodiments, the diol is selected from the group consisting of:benzene dimethanol and bisphenol-A.

In certain embodiments, provided are biobased polyethylene terephthalate(PET) derived from the biobased terephthalic acid compositions describedabove. In certain embodiments, provided is biobased polytrimethyleneterephthalate (PTT) derived from the biobased terephthalic acidcompositions described above. In certain embodiments, provided isbiobased polybutylene terephthalate (PBT) derived from the biobasedterephthalic acid compositions described above.

In certain embodiments, provided is biobased polyethylene isophthalate(PEI) derived from the biobased isophthalic acid compositions describedabove. In certain embodiments, provided is biobased polytrimethyleneisophthalate (PTI) derived from the biobased isophthalic acidcompositions described above. In certain embodiments, provided isbiobased polybutylene isophthalate (PBI) derived from the biobasedisophthalic acid compositions described above.

In certain embodiments, provided is biobased polyethylene isophthalatederived from the biobased isophthalic acid compositions described above.

Enumerated Embodiments

The following enumerated embodiments/claims are representative of someaspects of the invention.

-   1. A compound having the formula:

-   -   wherein Z is selected from the group consisting of —OR^(y), —Cl,        —Br, —NR^(y) ₂, and —SR^(y),        -   where, where each R^(y) is independently hydrogen, an            optionally substituted group selected the group consisting            of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic;            C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms independently            selected from the group consisting of nitrogen, oxygen, and            sulfur; 5- to 10-membered heteroaryl having 1-4 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic            having 1-2 heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur; an oxygen            protecting group; and a nitrogen protecting group; where two            R^(y) on a nitrogen atom may be taken with the nitrogen atom            to form an optionally substituted 4- to 7-membered            heterocyclic ring having 0-2 additional heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur.

-   2. The compound of embodiment 1, wherein Z is —OR^(y).

-   3. The compound of embodiment 2, wherein Z is —OH.

-   4. The compound of embodiment 3, wherein R^(Y) is C₁₋₂₀ aliphatic,    or where R^(y) is C₁₋₁₂ aliphatic, or where R^(y) is C₁₋₈ aliphatic,    or where R^(y) is C₁₋₆ aliphatic, or where R^(y) is C₁₋₄ aliphatic.

-   5. A method of making a compound of formula:

-   -   the method comprising the step of reacting furfural with an        alpha beta unsaturated acid,    -   where R^(y) is independently hydrogen, or an optionally        substituted moiety selected the group consisting of acyl;        arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀        heteroaliphatic having 1-4 heteroatoms independently selected        from the group consisting of nitrogen, oxygen, and sulfur; 5- to        10-membered heteroaryl having 1-4 heteroatoms independently        selected from the group consisting of nitrogen, oxygen, and        sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; and an oxygen protecting group.

-   5b. The method of embodiment 5, wherein the alpha beta unsaturated    acid has the formula:

-   6. The method of embodiment 5, wherein R^(y) is —H.-   7. The method of embodiment 5, wherein R^(y) is C₁₋₂₀ aliphatic, or    where R^(y) is C₁₋₁₂ aliphatic, or where R^(y) is C₁₋₈ aliphatic, or    where R^(y) is C₁₋₆ aliphatic, or where R^(y) is C₁₋₄ aliphatic.-   8. A method for the production of a compound of formula:

the method comprising the step of oxidizing a compound of formula:

-   -   where each R^(z) is independently selected from the group        consisting of: —H, R^(y), optionally substituted C₁₋₂₀        aliphatic, and optionally substituted aryl; and    -   R^(y) is independently hydrogen, or an optionally substituted        moiety selected the group consisting of acyl; arylalkyl; 6- to        10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having        1-4 heteroatoms independently selected from the group consisting        of nitrogen, oxygen, and sulfur; 5- to 10-membered heteroaryl        having 1-4 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; 4- to 7-membered        heterocyclic having 1-2 heteroatoms independently selected from        the group consisting of nitrogen, oxygen, and sulfur; and an        oxygen protecting group.

-   9. The method of embodiment 8, wherein R^(z) is —H.

-   10. The method of embodiment 8, wherein R^(z) is —CH₃.

-   11. The method of embodiment 8, wherein the compound of formula:

-   -   is produced by reaction of furfural with a compound having a        formula:

-   12. A isophthalic acid composition produced via cycloaddition    reaction of furfural with an alpha beta unsaturated carboxylic acid.-   13. The isophthalic acid composition of embodiment 12, characterized    in that the isophthalic acid is at least partially derived from a    biobased feedstock.-   14. The isophthalic acid composition of embodiment 13, wherein    carbon atoms one through five as shown in the formula:

-   -   are derived from biobased furfural.

-   15. The isophthalic acid composition of embodiment 13, wherein    carbon atoms six through eight as shown in the formula:

-   -   are derived from a biobased alpha beta unsaturated acid.

-   16. A biobased polymer composition derived from an isophthalic acid    composition of any of embodiments 12 through 15.

-   17. The biobased polymer composition of embodiment 16, wherein the    polymer comprises polyethylene isophthalate (PIT).

-   18. The biobased polymer composition of embodiment 17, wherein the    polyethylene isophthalate further comprises biobased ethylene    glycol.

-   19. A process for the production of biobased terephthalic acid or    derivatives thereof, the method comprising the steps of:    -   a) reacting ethylene oxide with carbon monoxide in one or more        steps to provide a product selected from acrylic acid and        acrylate ester;    -   b) reacting the product of step (a) with furfural to provide a        Diels Alder adduct;    -   c) oxidizing the Diels Alder adduct of step (b) to provide        product selected from isophthalic acid and isophthalate ester.    -   d) treating the product of step (c) to convert the isophthalic        acid to terephthalic acid.

-   20. The process of embodiment 2, wherein one or more steps are    performed in a continuous process.

-   21. The process of embodiment 2, characterized in that at least one    of the ethylene oxide, the carbon monoxide or the furfural is    biobased.

-   22. A method of making a compound of formula:

-   -   the method comprising the step of reacting furfural with beta        propiolactone,    -   where R^(y) is independently hydrogen, or an optionally        substituted moiety selected the group consisting of acyl;        arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀        heteroaliphatic having 1-4 heteroatoms independently selected        from the group consisting of nitrogen, oxygen, and sulfur; 5- to        10-membered heteroaryl having 1-4 heteroatoms independently        selected from the group consisting of nitrogen, oxygen, and        sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; and an oxygen protecting group.

-   23. The method of embodiment 22, wherein Ry is —H.

-   24. The method of embodiment 22, wherein Ry is C1-20 aliphatic, or    where Ry is C1-12 aliphatic, or where Ry is C1-8 aliphatic, or where    Ry is C1-6 aliphatic, or where Ry is C1-4 aliphatic.

-   25. The method of embodiment 24, wherein the step of reacting is    performed in the presence of a compound of formula R^(y) OH.

-   26. A method for the production of a compound of formula:

-   -   the method comprising the steps of reacting furfural with beta        propiolactone and oxidizing the resulting adduct,        -   where each R^(z) is independently selected from the group            consisting of:        -   hydrogen, or an optionally substituted moiety selected the            group consisting of acyl; arylalkyl; 6- to 10-membered aryl;            C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4            heteroatoms independently selected from the group consisting            of nitrogen, oxygen, and sulfur; 5- to 10-membered            heteroaryl having 1-4 heteroatoms independently selected            from the group consisting of nitrogen, oxygen, and sulfur;            4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; and an oxygen protecting            group.

-   27. The method of embodiment 26, wherein R^(z) is —H.

-   28. The method of embodiment 26, wherein R^(z) is —CH₃.

-   29. A method of making a compound of formula:

-   -   the method comprising the step of reacting furfural with beta        propiolactone,        -   where R^(y) is independently hydrogen, or an optionally            substituted moiety selected the group consisting of acyl;            arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀            heteroaliphatic having 1-4 heteroatoms independently            selected from the group consisting of nitrogen, oxygen, and            sulfur; 5- to 10-membered heteroaryl having 1-4 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic            having 1-2 heteroatoms independently selected from the group            consisting of nitrogen, oxygen, and sulfur; and an oxygen            protecting group.

-   30. The method of embodiment 29, wherein Ry is —H.

-   31. The method of embodiment 29, wherein Ry is C1-20 aliphatic, or    where Ry is C1-12 aliphatic, or where Ry is C₁₋₈ aliphatic, or where    R^(y) is C₁₋₆ aliphatic, or where R^(y) is C₁₋₄ aliphatic.

-   32. A method for the production of a compound of formula:

-   -   the method comprising the steps of reacting furfural with beta        propiolactone and oxidizing the resulting adduct,        -   where each R^(z) is independently selected from the group            consisting of:        -   hydrogen, or an optionally substituted moiety selected the            group consisting of acyl; arylalkyl; 6- to 10-membered aryl;            C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4            heteroatoms independently selected from the group consisting            of nitrogen, oxygen, and sulfur; 5- to 10-membered            heteroaryl having 1-4 heteroatoms independently selected            from the group consisting of nitrogen, oxygen, and sulfur;            4- to 7-membered heterocyclic having 1-2 heteroatoms            independently selected from the group consisting of            nitrogen, oxygen, and sulfur; and an oxygen protecting            group.

-   33. The method of embodiment 32, wherein Rz is —H.

-   34. The method of embodiment 32, wherein Rz is —CH3.

-   35. A process for the production of biobased terephthalic acid or    derivatives thereof, the method comprising the steps of:    -   a) reacting ethylene oxide with carbon monoxide in one or more        steps to provide beta propiolactone;    -   b) reacting the product of step (a) with furfural to provide an        adduct selected from the group consisting of:

and mixtures of both of these;

-   -   c) oxidizing the adduct of step (b) to provide product selected        from phthalic acid, phthalic acid ester, isophthalic acid and        isophthalate ester.    -   d) treating the product of step (c) to convert the phthalic of        isophthalic acid to terephthalic acid.

-   36. The process of embodiment 35, wherein one or more steps are    performed in a continuous process.

-   37. The process of embodiment 35, characterized in that at least one    of the ethylene oxide, the carbon monoxide or the furfural is    biobased.

-   38. A method, comprising:    -   continuously feeding a first reaction zone with furfural and a        compound of formula:

-   -   wherein R^(y) is independently hydrogen, or an optionally        substituted moiety selected the group consisting of acyl;        arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀        heteroaliphatic having 1-4 heteroatoms independently selected        from the group consisting of nitrogen, oxygen, and sulfur; 5- to        10-membered heteroaryl having 1-4 heteroatoms independently        selected from the group consisting of nitrogen, oxygen, and        sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; and an oxygen protecting group,        to provide a first product stream comprising a first product of        formula:

-   -   continuously feeding the first product stream to an oxidizing        reaction zone where the first product is contacted with air to        form a second product stream comprising a second product having        formula:

-   -   wherein each R^(z) is independently selected from the group        consisting of —H, R^(y), optionally substituted C₁₋₂₀ aliphatic,        and optionally substituted aryl; and    -   continuously feeding the second product stream to a        rearrangement reaction zone where        the second product is converted to the compound of formula:

-   39. A method, comprising:    -   continuously feeding a first reaction zone with furfural and        beta propiolactone, and optionally an alcohol of formula        HOR^(y), to provide a first product stream comprising a first        product having formula:

-   -   where R^(y) is independently hydrogen, or an optionally        substituted moiety selected the group consisting of acyl;        arylalkyl; 6- to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀        heteroaliphatic having 1-4 heteroatoms independently selected        from the group consisting of nitrogen, oxygen, and sulfur; 5- to        10 membered heteroaryl having 1-4 heteroatoms independently        selected from the group consisting of nitrogen, oxygen, and        sulfur; 4- to 7-membered heterocyclic having 1-2 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; and an oxygen protecting group; and;    -   continuously feeding the first product stream to an oxidizing        reaction zone where the first product is contacted with air to        form a second product stream comprising a second product having        formula:

-   -   wherein each R^(z) is independently selected from the group        consisting of —H, R^(y), optionally substituted C₁₋₂₀ aliphatic,        and optionally substituted aryl; and    -   continuously feeding the second product stream to a        rearrangement reaction zone where the second product is        converted to the compound of formula:

-   40. The method of embodiment 38 or 39, wherein R^(y) is —H.-   41. The method of embodiment 38 or 39, wherein Ry is C1-20    aliphatic.-   42. The method of any one of embodiments 38 to 41, wherein Rz is —H.-   43. The method of any one of embodiments 38 to 41, wherein Rz is    —CH3.-   44. An isophthalic acid composition produced via cycloaddition    reaction of furfural with an alpha beta unsaturated carboxylic acid,    wherein the isophthalic acid is at least partially derived from a    biobased feedstock.-   45. An isophthalic acid composition produced via reaction of    furfural with beta propiolactone, wherein the isophthalic acid is at    least partially derived from a biobased feedstock.-   46. The isophthalic acid composition of embodiment 44 or 45, wherein    carbon atoms one through five as shown in the formula:

are derived from biobased furfural.

-   47. The isophthalic acid composition of embodiment 44, wherein    carbon atoms six through eight as shown in the formula:

are derived from a biobased alpha beta unsaturated acid.

-   48. The isophthalic acid composition of embodiment 45, wherein    carbon atoms six through eight as shown in the formula:

are derived from a biobased beta propiolactone.

-   49. A biobased polymer composition derived from an isophthalic acid    composition of any one of embodiments 44 to 48.-   50. The biobased polymer composition of embodiment 49, wherein the    polymer comprises polyethylene isophthalate (PIT).-   51. The biobased polymer composition of embodiment 50, wherein the    polyethylene isophthalate further comprises biobased ethylene    glycol.-   52. A method for the production of biobased terephthalic acid,    comprising:    -   a) reacting ethylene oxide with carbon monoxide to provide a        product selected from beta propiolactone, acrylic acid and        acrylate ester;    -   b) reacting the product of step (a) with furfural to provide a        Diels Alder adduct;    -   c) oxidizing the Diels Alder adduct of step (b) to provide        product selected from isophthalic acid and isophthalate ester;        and    -   d) treating the product of (c) to convert the isophthalic acid        to terephthalic acid.-   53. The method of embodiment 52, wherein one or more steps are    performed in a continuous process.-   54. The method of embodiment 52 or 53, wherein at least one of the    ethylene oxide, the carbon monoxide or the furfural is biobased.

What is claimed is:
 1. A method for the production of a compound offormula:

the method comprising the step of oxidizing a compound of formula:

wherein each R^(z) is selected from the group consisting of: —H, R^(y),optionally substituted C₁₋₂₀ aliphatic, and optionally substituted aryl;and R^(y) is hydrogen, or an optionally substituted moiety selected thegroup consisting of acyl; arylalkyl; 6- to 10-membered aryl; C₁₋₂₀aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms selected fromthe group consisting of nitrogen, oxygen, and sulfur; 5- to 10-memberedheteroaryl having 1-4 heteroatoms selected from the group consisting ofnitrogen, oxygen, and sulfur; 4- to 7-membered heterocyclic having 1-2heteroatoms selected from the group consisting of nitrogen, oxygen, andsulfur; and an oxygen protecting group.
 2. The method of claim 1,wherein each R^(z) is —H.
 3. The method of claim 1, wherein each R^(z)is —CH3.
 4. The method of claim 1, wherein the compound of formula:

is produced by reaction of furfural with a compound having a formula:


5. A method for the production of a compound of formula:

the method comprising the steps of reacting furfural with betapropiolactone and oxidizing the resulting adduct, where each R^(z) isselected from the group consisting of: hydrogen, or an optionallysubstituted moiety selected the group consisting of acyl; arylalkyl; 6-to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4heteroatoms selected from the group consisting of nitrogen, oxygen, andsulfur; 5- to 10-membered heteroaryl having 1-4 heteroatoms selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms selected from the groupconsisting of nitrogen, oxygen, and sulfur; and an oxygen protectinggroup.
 6. The method of claim 5, wherein each R^(z) is —H.
 7. The methodof claim 5, wherein each R^(z) is —CH3.
 8. A method for the productionof a compound of formula:

the method comprising the steps of reacting furfural with betapropiolactone and oxidizing the resulting adduct, where each R^(z) isselected from the group consisting of: hydrogen, or an optionallysubstituted moiety selected the group consisting of acyl; arylalkyl; 6-to 10-membered aryl; C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4heteroatoms selected from the group consisting of nitrogen, oxygen, andsulfur; 5- to 10-membered heteroaryl having 1-4 heteroatoms selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 4- to7-membered heterocyclic having 1-2 heteroatoms selected from the groupconsisting of nitrogen, oxygen, and sulfur; and an oxygen protectinggroup.
 9. The method of claim 8, wherein each R^(z) is —H.
 10. Themethod of claim 8, wherein each R^(z) is —CH3.
 11. An isophthalic acidcomposition produced via cycloaddition reaction of furfural with analpha beta unsaturated carboxylic acid, wherein the isophthalic acid isat least partially derived from a biobased feedstock.
 12. Theisophthalic acid composition of claim 11, wherein carbon atoms onethrough five as shown in the formula:

are derived from biobased furfural.
 13. An isophthalic acid compositionproduced via reaction of furfural with beta propiolactone, wherein theisophthalic acid is at least partially derived from a biobasedfeedstock.
 14. The isophthalic acid composition of claim 13, whereincarbon atoms one through five as shown in the formula:

are derived from biobased furfural.
 15. The isophthalic acid compositionof claim 11, wherein carbon atoms six through eight as shown in theformula:

are derived from a biobased alpha beta unsaturated acid.
 16. Theisophthalic acid composition of claim 13, wherein carbon atoms sixthrough eight as shown in the formula:

are derived from a biobased beta propiolactone.
 17. A biobased polymercomposition derived from an isophthalic acid composition of claim 11.18. The biobased polymer composition of claim 17, wherein the polymercomprises polyethylene isophthalate (PIT).
 19. The biobased polymercomposition of claim 18, wherein the polyethylene isophthalate furthercomprises biobased ethylene glycol.
 20. A method for the production ofbiobased phthalic acid or an ester thereof, comprising: a. reactingethylene oxide with carbon monoxide to provide a product selected frombeta propiolactone, acrylic acid and acrylate ester; b. reacting theproduct of step (a) with furfural to provide a Diels Alder adduct; andc. oxidizing the Diels Alder adduct of step (b) to provide a productselected from phthalic acid and phthalate ester.
 21. The method of claim20, wherein at least one of the ethylene oxide, the carbon monoxide orthe furfural is biobased.
 22. A method for the production of biobasedisophthalic acid or an ester thereof, comprising: a. reacting ethyleneoxide with carbon monoxide to provide a product selected from betapropiolactone, acrylic acid and acrylate ester; b. reacting the productof step (a) with furfural to provide a Diels Alder adduct; and c.oxidizing the Diels Alder adduct of step (b) to provide a productselected from isophthalic acid and isophthalate ester.
 23. The method ofclaim 22, wherein at least one of the ethylene oxide, the carbonmonoxide or the furfural is biobased.
 24. A method, comprising: feedinga first reaction zone with furfural and a compound of formula:

wherein R^(y) is hydrogen, or an optionally substituted moiety selectedfrom the group consisting of acyl; arylalkyl; 6- to 10-membered aryl;C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 5- to10-membered heteroaryl having 1-4 heteroatoms selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms selected from the group consistingof nitrogen, oxygen, and sulfur; and an oxygen protecting group, toprovide a first product stream comprising a first product of formula:

feeding the first product stream to an oxidizing reaction zone where thefirst product is contacted with air to form a second product streamcomprising a second product having formula:

wherein each R^(z) is selected from the group consisting of —H, R^(y),optionally substituted C₁₋₂₀ aliphatic, and optionally substituted aryl;and continuously feeding the second product stream to a rearrangementreaction zone where the second product is converted to a compound offormula:


25. The method of claim 24 wherein R^(y) is —H.
 26. The method of claim24 wherein R^(y) is C₁₋₂₀ aliphatic.
 27. The method of claim 24 whereineach R^(z) is —H.
 28. The method of claim 24 wherein each R^(z) is —CH₃.29. A method, comprising: feeding a first reaction zone with furfuraland beta propiolactone, and an alcohol of formula HOR^(y), to provide afirst product stream comprising a first product having formula:

wherein R^(y) is hydrogen, or an optionally substituted moiety selectedfrom the group consisting of acyl; arylalkyl; 6- to 10-membered aryl;C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms selectedfrom the group consisting of nitrogen, oxygen, and sulfur; 5- to10-membered heteroaryl having 1-4 heteroatoms selected from the groupconsisting of nitrogen, oxygen, and sulfur; 4- to 7-memberedheterocyclic having 1-2 heteroatoms selected from the group consistingof nitrogen, oxygen, and sulfur; and an oxygen protecting group; and;feeding the first product stream to an oxidizing reaction zone where thefirst product is contacted with air to form a second product streamcomprising a second product having formula:

wherein each R^(z) is selected from the group consisting of —H, R^(y),optionally substituted C₁₋₂₀ aliphatic, and optionally substituted aryl;and feeding the second product stream to a rearrangement reaction zonewhere the second product is converted to a compound of formula:


30. The method of claim 29, wherein R^(y) is —H.
 31. The method of claim29, wherein R^(y) is C₁₋₂₀ aliphatic.
 32. The method of claim 29,wherein each R^(z) is —H.
 33. The method of claim 29, wherein each R^(z)is —CH₃.